Skip to content
naulon
Get started

No retraction, correction or concern found when last checked on Oct 19, 2026.

Interleukin-17A and Keratinocytes in Psoriasis

Masutaka Furue, Kazuhisa Furue, Gaku Tsuji and 1 more

International Journal of Molecular Sciences · 2020 · Review · CC BY

doi:10.3390/ijms21041275

Abstract

The excellent clinical efficacy of anti-interleukin 17A (IL-17A) biologics on psoriasis indicates a crucial pathogenic role of IL-17A in this autoinflammatory skin disease. IL-17A accelerates the proliferation of epidermal keratinocytes. Keratinocytes produce a myriad of antimicrobial peptides and chemokines, such as CXCL1, CXCL2, CXCL8, and CCL20. Antimicrobial peptides enhance skin inflammation. IL-17A is capable of upregulating the production of these chemokines and antimicrobial peptides in keratinocytes. CXCL1, CXCL2, and CXCL8 recruit neutrophils and CCL20 chemoattracts IL-17A-producing CCR6+ immune cells, which further contributes to forming an IL-17A-rich milieu. This feed-forward pathogenic process results in characteristic histopathological features, such as epidermal hyperproliferation, intraepidermal neutrophilic microabscess, and dermal CCR6+ cell infiltration. In this review, we focus on IL-17A and keratinocyte interaction regarding psoriasis pathogenesis.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 19, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

Psoriasis is an immune-mediated chronic skin disease characterized by epidermal hyperproliferation, an intraepidermal accumulation of neutrophils, and dermal inflammatory cell infiltrates that are composed of dendritic cells and T cells. It has an estimated global prevalence of 2–4%. Males are twice as likely as females to be affected. As desquamative erythema can affect any skin site, psoriasis profoundly impairs the patients’ quality of life, treatment satisfaction and adherence, and socioeconomic stability. The skin lesion usually appears on the sites with frequent trauma such as elbows and knees. This injury-induced development of psoriasis is called Koebner phenomenon. Environmental factors, such as smoking, also trigger or exacerbate psoriatic lesions. Genetic factors are critically involved in the development of psoriasis. In addition to skin eruption, approximately 30% of patients with psoriasis manifest psoriatic arthritis. Psoriasis is also significantly comorbid with other autoimmune diseases, such as bullous pemphigoid. Psoriasis is frequently associated with cardiovascular diseases, metabolic diseases, and renal disorders. Cancer risk is slightly higher in patients with psoriasis. The topical application of steroids and vitamin D3 analogues inhibits psoriatic inflammation and normalizes epidermal differentiation. Systemic treatments, such as methotrexate, cyclosporine, phototherapy, and the phosphodiesterase 4 inhibitor apremilast, are useful for patients with extensive lesions.

That the tumor necrosis factor-α (TNF-α) and IL-23/IL-17A axes appear to be major drivers in the pathogenesis of psoriasis is underscored by the excellent response of psoriasis to biologics targeting TNF-α, IL-23, and IL-17A, although a difference exists in their efficacy. Anti-TNF-α/IL-23/IL-17A biologics successfully improve psoriatic arthritis. Reductions in comorbid cardiovascular events and systemic inflammation have been reported in patients with psoriasis treated with anti-TNF/IL23/IL17 biologics.

As the clinical response to anti-IL-23/IL-17A biologics seems better than that to anti-TNF-α biologics in psoriasis, the IL-23/IL-17A axis likely plays a more crucial role than the TNF-α axis in the development of psoriasis. Under the regulation of IL-23p19, IL-17A-producing CD4+ helper T (Th17) cells create a self-amplifying, feed-forward inflammatory response that is markedly augmented in the presence of TNF-α. In addition, Th17 cells produce high amounts of TNF-α. Therefore, IL-17A inhibition by the anti-IL-17A biologic results in early clinical, histopathologic, and molecular resolution of psoriasis.

In addition, various murine psoriasis models stress a pivotal role of the IL-23/IL-17A axis in experimental psoriasis. Multiple animal studies have indicated that the interaction between IL-17A and keratinocyte is the key issue in the development of psoriasis. In parallel, the importance of IL-17A and keratinocyte interaction is reinforced in patients with psoriasis who are successfully treated with the anti-IL-17A biologic. In this review, we will focus on the multifaceted biological response in keratinocytes stimulated by IL-17A with regard to psoriatic pathogenesis.

2. IL-17A Signaling System

The IL-17 family plays a critical role in the immune response in infectious, inflammatory, autoimmune, and neoplastic disorders. The IL-17 family and its receptors are evolutionally ancient, and they are present in species as early as lamprey and sea urchins. IL-17 family members comprise IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, IL-17F, and IL-17AF. IL-17AF is a hybrid heterodimer of IL-17A and IL-17F. IL-17E is also called IL-25 and is related to the type 2 immune response and allergies. Among IL-17 family members, IL-17A has been the most strongly implicated in human health and disease. IL-17A is produced from hematopoietic cells, including Th17, CD8+ cytotoxic T cell (Tc17), γδ T cell, natural killer cell, group 3 innate lymphoid cell (ILC3), and “natural” Th17 cell, but IL-17B, IL-17C, and IL-25 are preferentially produced from nonhematopoietic cells, including keratinocytes. Both hematopoietic cells and keratinocytes produce IL-17F. Keratinocyte-derived IL-17C is capable of stimulating Th17 cells to secrete more IL-17A.

The IL-17 receptor (IL-17R) is composed of five members: IL-17RA, IL-17RB, IL-17RC, IL-17RD, and IL-17RE. IL-17A, IL-17F, and IL-17AF all share the same IL-17R comprising IL-17RA and IL-17RC heterodimers. IL-17C binds to IL-17RA and IL-17RE heterodimers. IL-25 ligates IL-17RA and IL-17RB. A recent study showed that IL-17A also activates IL-17RA and IL-17RD heterodimers (Figure 1). IL-17B binds IL-17RB, but another heterodimeric IL-17R member remains unidentified. Keratinocytes express both IL-17RA/IL-17RC and IL-17RA/IL-17RD, and the binding of IL-17A induces the transcription of differential gene sets. Initial subcellular events in the ligation of IL-17RA/RC by IL-17A are the recruitment and activation of ACT1 encoded by the TRAF3IP2 gene, TRAF6 and CARMA2 complexes, and the downstream activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and MAPKs. The ligation of IL-17RA/IL-17RC by IL-17A induces the activation of NF-κB, ERK, p38 MAPK, and JNK, while that of IL-17RA/IL-17-RD mainly activates p38 MAPK and JNK and barely affects NF-κB and ERK. In addition, IL-17RA physically and functionally interacts with and transactivates epidermal growth factor (EGFR). IL-17RD potentially interacts with and transactivates fibroblast growth factor 2 receptor.

In addition to the above-mentioned signaling cascades, IL-17A activates various other signal molecules including signal transducer and activator of transcription 3 (STAT3) in keratinocytes. STAT3 is a very crucial signaling molecule in the development of psoriasis because transgenic mice with keratinocytes expressing a constitutively active Stat3 (K5.Stat3C mice) develop a skin phenotype either spontaneously, or in response to wounding, that closely resembles psoriasis. Moreover, a STAT3 inhibitor STA-21 inhibits the generation of skin lesion in these psoriatic mice. IL-17A is known to activate STAT3 via receptor-interacting protein 4 (RIP4) activation and upregulates the CCL20 expression. IL-17A also upregulates keratin 17 expression via STAT1 and STAT3 activation. IL-6 and IL-22 also play a synergistic role in development of psoriasis with IL-17A. Notably, both IL-6 and IL-22 are potent STAT3 activators. In accordance, biological or natural molecules such as indirubin and its derivatives useful for inactivating STAT3 exhibit therapeutic potential for psoriasis (Figure 2). It reveals that IL-17 and IL-22 promote keratinocyte stemness and potentiate its regeneration. IL-6 is produced from keratinocytes in response to IL-17A. IL-22 is produced from Th17/22 cells, Th22 cells, and other immune cells.

In humans, impairment of the IL-17 signal causes infectious diseases, especially by Candida albicans, which is a ubiquitous fungus and commensal yeast of the intestines and skin. Notably, deficiency of the IL17RA, IL17RC, IL17F, or TRAF3IP2 genes is implicated in chronic mucocutaneous candidiasis disease (CMCD), which is characterized by recurrent or persistent infection affecting the nails, skin, and oral and genital mucosae caused by the Candida species, often C. albicans. Impairment of the IL-17 signal is evident in other immunocompromised inborn errors, including autosomal-dominant hyper IgE syndrome, autosomal dominant STAT1 gain-of-function, autosomal-recessive autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), autosomal-recessive CARD9 deficiency, IL12RB1 deficiency, IL12B deficiency, and RORC deficiency. However, these inborn errors seem to exhibit more complicated immune defects beyond IL-17 dysfunction and manifest CMCD together with other types of infection, including Mycobacterium, Staphylococcus, and viral disorders. Of note, mice lacking Traf3ip2 (Act1) or Il17ra manifest similar clinical phenotype as human CMCD patients lacking IL17RA or IL17RC. A recent murine study by Sparber et al. also indicates that Malassezia infection selectively triggers the IL-17A-induced immune response. These findings indicate a crucial role of IL-17A in anti-fungal immunity in humans and mice.

Mice overexpressing IL-17A in keratinocytes (K14-IL-17Aind/+ mice) exhibit severe psoriasiform skin inflammation and vascular dysfunction in conjunction with infiltration of the vasculature by inflammatory myeloid cells. The K14-IL-17Aind/+ mice acquire the highest local and systemic IL-17A levels and exhibit a particularly severe psoriasis-like skin phenotype. Homozygous CD11c-IL-17Aind/ind mice and heterozygous CD11c-IL-17A ind/+ mice show a delayed onset of moderate to severe psoriasis-like skin disease associated with reduced amounts of cutaneous IL-17A compared with K14-IL-17Aind/+ mice. In agreement with elevated skin and a stepwise increase in systemic IL-17A, homozygous CD11c-IL-17A ind/ind mice develop earlier and more severe skin lesions, as well as more pronounced vascular inflammation and dysfunction than heterozygous CD11c-IL-17A ind/+ mice. These experimental models indicate that IL-17A induces psoriasis-like lesions in a dose-dependent manner, irrespective of its cellular source.

3. IL-17A and Psoriasis

In the early 2000s, IL-23 was found to induce the production of IL-17A by activated CD4+ T cells, which were later named Th17 cells. These cells express RORγt (RORC) as the master transcription factor and promoted the anti-infectious defense in the mucosa and skin, whereas excessive exposure to IL-23 induces their transformation into autoimmune or autoinflammatory immune cells. Accordingly, the intradermal injection of IL-23 induces murine psoriasis-like dermatitis with epidermal acanthosis, neutrophil recruitment, and the infiltration of IL-17-producing T cells.

Psoriasis is one of the most typical IL-23/IL-17A-driven human diseases. Th17 cells, Tc17 cells, IL-17-producing γδ T cells, and ILC3 can all be found in psoriatic skin. IL-23 is composed of IL-23p40 and IL-23p19 subunits, and the expression of both is upregulated in the lesional skin compared to the nonlesional skin in psoriasis. Dermal dendritic cells and monocytes are major sources of IL-23 production. However, immunohistological staining also proves that IL23p40 and IL23p19 are expressed in normal and psoriatic keratinocytes. Moreover, the epidermal expression of IL-23p40 and IL-23p19 is stronger in psoriasis lesions than in healthy controls. Murine keratinocytes also produce biologically active IL-23. IL-23 can promote keratinocyte growth and histological acanthosis via the JAK2/AKT/STAT3/LMO4 signaling pathway. LIM-domain only protein 4 (LMO4) is a LIM-domain protein that regulates keratinocyte proliferation and differentiation during embryogenesis. In addition, TNF-α is an active stimulator of IL-23 production from keratinocytes in mice and possibly in humans. In parallel, the anti-IL-23p40 antibody (Ustekinumab) and anti-IL-23p19 antibodies (guselkumab, risankizumab, and tildrakizumab) exhibit a high efficacy to psoriasis with a superiority of risankizumab over ustekinumab, and guselkumab over the anti-TNF-α antibody adalimumab.

The expression of IL17A, IL17F, and IL17C is upregulated in psoriatic lesional skin. The intradermal injection of IL17C induces epidermal thickening and neutrophil infiltration. As significant efficacy of the anti-IL17C antibody has recently been noted in murine psoriasis and atopic dermatitis, its human use has been suggested. However, IL-17A is believed to be the most pathogenic IL-17 family member in psoriasis. The lesional skin of psoriasis harbors IL-17A-producing immune cells, and transcriptomic analysis indicates a clear predominance of IL-17A signals. Subsets of IL-17A-producing T cells are reactive to autoantigens, such as LL-37 (cathelicidin), a disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5), keratin 17, and neolipid antigens generated by phospholipase A2 group IV D (PLA2G4D). IL-17A-dominant immune activation is also detected in the nonlesional skin of psoriasis.

There are three commercially available anti-IL17A biologics: secukinumab (fully human IgG1κ anti-IL17A antibody), ixekizumab (fully human IgG4 anti-IL17A antibody), and brodalumab (fully human IgG2 anti-IL17RA antibody). The severity of psoriatic skin lesions is generally evaluated by the Psoriasis Area and Severity Index (PASI). The efficacy of a therapeutic agent is assessed by the rate of responders who achieve 75%, 90%, and 100% reduction of PASI, namely, PASI75, PASI90, and PASI100, respectively. All three anti-IL-17A biologics exbibit remarkable therapeutic efficacy for psoriasis. The PASI90 scores of secukinumab, ixekizumab, and brodalumab are reported to be as high as 60% to 70% at 12 weeks post treatment.

Regarding histology, the psoriatic epidermis is acanthotic and the proliferating capacity of keratinocyte is increased as determined by Ki67 positivity and cytokeratin 16 expression. In accordance with the accumulation of neutrophils in psoriasis, the gene expression of neutrophilic cytochemokines CXCL1, CXCL2, CXCL8, and IL-36 is upregulated in the lesional skin of psoriasis. Psoriatic keratinocytes produce a large amount of CCL20, which is a potent chemoattractant for CCR6+ IL-17A-producing Th17, ILC3, Tc17, and γδ T cells. Interestingly, IL-17A actively upregulates the production of these key cytochemokines as well as proliferative capacity in keratinocytes.

4. IL-17A and Keratinocyte Proliferation/Differentiation

Psoriatic keratinocytes simultaneously exhibit increased proliferation (Ki67+ or cytokeratin 16+ cell number) and differentiation [involucrin (IVL)+ cell number]. Accordingly, IL17A is an active promoter of keratinocyte proliferation and differentiation. In psoriasis patients, the neutralization of IL-17A by ixekizumab or secukinumab significantly decreases histological acanthosis, the number of Ki-67+-proliferating keratinocytes, and epidermal cytokeratin 16 expression. In the murine imiquimod-induced psoriasis model, topical imiquimod induces epidermal thickening that is significantly alleviated in Traf3ip2 (Act1)-deficient mice in which IL-17 signaling is blocked. The molecular mechanisms of the IL-17A-mediated acceleration of keratinocyte proliferation and differentiation are not yet fully understood.

IL-17A alone is likely to be insufficient to evoke a significant inflammatory response and may cooperatively or synergistically accelerate the proinflammatory cascade in combination with other cytokines, such as TNF-α, IL-23, IL-1β, IL-6, IL-22 and transforming growth factor-β (TGF-β). Transcriptomic analysis reveals a clear additive or synergistic gene regulation by IL-17A and TNF-α in human keratinocytes. This gene regulation is likely attributable to two sets of transcription factors: NF-κB and the C/CAAT-enhancer-binding proteins (C/EBP), C/EBPβ, or C/EBPδ. TNF-α is a strong inducer of active NF-κB, while IL-17A activates C/EBPβ or C/EBPδ and to a lesser extent NF-κB. Therefore, the IL-17A blockade reduces the expression of these responsive genes to a greater extent than TNF-α inhibition.

The C/EBP family members are highly expressed transcription factors in epidermal keratinocytes and sebocytes in mice and humans and accelerate their differentiation. The expression of C/EBPβ protein is located in the upper spinous layer and is strongly upregulated in the lesional skin of psoriasis. Together with the elevated gene expression of CEBPB, the expression of keratinocyte-terminal differentiation genes, such as IVL, FLG2, and TGM1, is upregulated in the lesional skin of psoriasis. In the promoter region of the IVL gene, there is a binding site for C/EBP, and the C/EBP transcription factor is necessary for the appropriate and continuous production of IVL protein. These results suggest that IL-17A accelerates keratinocyte differentiation by increasing C/EBPβ protein in keratinocytes.

Regarding keratinocyte proliferation, IL-17A stimulates keratinocytes to produce IL-19. The combination of IL-17 and TNF-α results in the synergistic expression of IL-19 in keratinocytes. IL-17 alone promotes IL-19 expression by approximately 1.79-fold, and TNF-α alone slightly reduces IL-19 expression, whereas a combination of IL-17 and TNF-α promotes expression by 54.6-fold. IL-19 itself promotes keratinocyte migration but not proliferation. However, it activates fibroblasts to produce keratinocyte growth factor, which upregulates keratinocyte proliferation. Additionally, the upregulation of cell cycle-related genes, such as CCNE1, CDCA5, and CDCA25A, suggests a direct contribution of IL-17 to epidermal KC proliferation. The expression of cytokeratin 16 is upregulated in the lesional epidermis of psoriasis patients and in keratinocytes incubated with IL-17A. The expression of cytokeratin 16 increases the proliferative capacity of keratinocytes via EGFR phosphorylation.

Other studies also underpin a possibility that IL-17A activates EGFR. Chen et al. have demonstrated that IL-17A transactivates EGFR in keratinocyte stem cells. IL-17A accelerates the enzymatic cleavage of amphiregulin, which activates EGFR in airway epithelial cells. In the lesional skin of psoriasis, the expression of EGFR ligands, such as heparin-binding EGF, transforming growth factor-α, and amphiregulin, is overexpressed. Consistent with these notions, the inhibition of EGFR by erlotinib or cetuximab successfully improves severe psoriasis. These studies suggest that EGFR activation may partly explain the IL-17A-mediated upregulation of keratinocyte proliferation.

5. IL-17A and Cyto/Chemokines in Keratinocytes

In keratinocytes, IL-17A upregulates the expression of various psoriasis-related cyto/chemokines and antimicrobial peptides, such as CXCL1, CXCL8, IL-36G, CCL20, IL-19, IL-17C, S100A7, S100A8, S100A9, LL-37, and defensin β 4A (DEFB4A). The expression of these molecules is upregulated in the lesional skin of psoriasis and is downregulated to normal levels by biologics targeting TNF-α or IL-17A. Some are upregulated even in the nonlesional skin of patients with psoriasis. The IL-17A-induced upregulation of these molecules is further amplified in the presence of TNF-α and IL-19.

CXCL1 and CXCL8 are potent chemoattractants for neutrophils. IL-36G induces CXCL1 and CXCL8 expression in an autocrine fashion in keratinocytes and recruits neutrophils. Full-length IL-36G is cleaved by cathepsin G released from infiltrated neutrophils, and the cleaved IL-36G exhibits a more potent functional activity than the full-length one. Moreover, IL-17A upregulates IL-36G production more potently in human psoriasis-derived keratinocytes than in healthy keratinocytes. Therefore, the IL-17A, IL-36G, CXCL1/CXCL8, and neutrophils form a feed-forward vicious cycle, and an intraepidermal neutrophilic microabscess (Munro’s microabscess or Kogoj’s spongiform pustule) may develop. The pathogenic significance of IL-36 is stressed more in pustular rather than plaque psoriasis. In parallel, inhibition of the IL-36 pathway is efficacious for the treatment of pustular psoriasis.

While most chemokines redundantly bind to multiple receptors, CCL20 has only one known receptor, CCR6. CCR6 is expressed on dendritic cells and IL-17-producing immune cells, including Th17, ILC3, Tc17, and γδ T cells. CCR6 is now considered a representative marker for Th17 cells. The human psoriatic epidermis expresses abundant CCL20 with the dermal infiltration of CCR6+ dendritic cells and skin-homing T cells. Although dermal dendritic cells and T cells express CCL20 in the psoriatic dermis, the expression of CCL20 is largely confined to the psoriatic epidermis, suggesting that epidermal keratinocytes are the major source of CCL20 production in psoriatic lesions. CCL20 is constitutively expressed in cultured keratinocytes, and its production is upregulated by TNF-α and IL-17A. Scratch injury upregulates the gene expression of CCL20, CXCL8, and IL36G, which may be related to the scratch-induced Koebner phenomenon frequently observed in patients with psoriasis. Preclinical studies have revealed that the humanized anti-CCR6 antibody efficiently inhibits the cutaneous infiltration of CCR6+ T cells in human and murine models. The development of small molecule inhibitors against CCR6 is also ongoing. Targeting the CCL20/CCR6 axis may be a potential therapeutic strategy for the treatment of psoriasis.

6. IL-17A and Anti-Microbial Peptides in Keratinocytes

S100A7, S100A8, S100A9, LL-37, and DEFB4A are anti-microbial peptides, and their expression is upregulated by IL-17A in keratinocytes. S100A7 (psoriasin) has a multifaceted role in keratinocyte pathophysiology, including wound healing, keratinocyte differentiation, nucleocytoplasmic transport, and chemotaxis for CD4+ T cells, neutrophils, and monocytes. The production of S100A7 is augmented in the presence of IL-19, IL-36G, and TNF-α. S100A8, S100A9, and S100A12 are alternatively known as calgranulin A, B, and C, respectively, and exhibit antimicrobial activity. All are elevated in psoriatic plaque and decreased by treatment with anti-IL-17A antibody secukinumab. The S100 family members primarily form homodimers or higher-order oligomers, but S100A8 and S100A9 uniquely form heterodimeric complexes, which are known as calprotectin. The chelation of Zn2+ and Mn2+ by extracellular S100A8/A9 is a proposed mechanism of antimicrobial activity. S100A12 also has a chemotactic activity for mast cells and monocytes. Pure human S100A8/A9 has broad spectrum antimicrobial activities against microorganisms, including Capnocytophaga sputigena, C. albicans, Escherichia coli, Staphylococcus aureus, S. epidermis, Borrelia burgdorferi, and Listeria monocytogenes, in vitro, and S100A12 has antimicrobial activity against filarial parasites. The receptor for advanced glycation end-products (RAGE) may serve as a common receptor for S100 proteins, including S100A7, S100A8, S100A9, and S100A12. S100A8/S100A9 augments the production of CXCL1, CXCL2, CXCL3, CXCL8, CCL20, IL-6, and TNF-α in keratinocytes, and it enhances keratinocyte proliferation. The transcriptional co-activator IκBζ, encoded by the NFKBIZ gene, plays a critical role in IL-17A-, IL-17F-, and IL-17A/F-mediated signaling, such as the gene expression of S100A7 and CCL20.

LL-37 is an antimicrobial peptide of human cathelicidin that is produced when keratinocytes are injured by a broad range of bacteria, viruses, and fungi. In addition to antimicrobial peptide activity, LL-37 exhibits “alarmin” function, affects adenosine triphosphate-receptor P2X7 and Toll-like receptor (TLR) signaling, and EGFR transactivation or intracellular Ca2+ mobilization. The released LL-37 binds to the infiltrated neutrophils. Neutrophils are a rich source of extracellular DNA due to their neutrophil extracellular traps. Upon stimulation with complexes of host DNA and LL-37, plasmacytoid dendritic cells produce large amounts of IFN-α. Notably, LL-37 induced the proliferation of circulating CD3+ T cells in 24 out of 52 patients with psoriasis (46%); therefore, LL-37 is effective for autoantigens. In total, 50 LL-37-reactive CD3+ T cells, including both CD4+ and CD8+ T cells, express the skin-homing receptor cutaneous lymphocyte antigen. LL-37 peptides bind to HLA-DR in dendritic cells and are presented to CD4+ T cells, while LL-37 peptides and the HLA-C*0602 complex activate CD8+ T cells. The majority of LL-37-reactive CD3+ T cells produce IL-17, and the capacity of their IL-17 production is associated with disease severity. Interestingly, the LL-37-specific IL-17-producing T cells are exclusively CD4+, whereas the LL-37-specific CD8+ T cells do not produce IL-17. A recent study by Takahashi et al. revealed that LL-37 can bind to self-RNA and stimulate macrophages to produce IL-6 via a scavenger receptor.

DEFB4A is highly expressed in psoriasis plaques and is the most psoriasis-specific antimicrobial peptide. In contrast, DEFB4A is expressed at negligible or low levels in normal skin and skin lesions of eczema. The expression of DEFB4A is upregulated by IL-17A and synergistically by IL-17A and TNF-α. The serum levels of DEFB4A are highly specific biomarkers for disease activity in patients with psoriasis. The number of neutrophil extracellular traps increase in psoriasis and upregulate the expression of DEFB4A. Notably, DEFB4A is a functional (non-chemokine) ligand for CCR6 and feasibly attracts Th17 cells.

Although the biological implications of increased antimicrobial peptides in psoriasis remain obscure, they are intimately associated with IL-17A-rich milieu. Therefore, the upregulated expression of these antimicrobial peptides is rapidly normalized by the neutralization of IL-17A by ixekizumab or secukinumab.

7. Conclusions

IL-17A is a multifunctional cytokine produced from adaptive and innate immune cells, such as Th17 and ILC3s. It orchestrates and promotes the peripheral tissue defense system against microbial insult, especially fungal infection. Psoriasis is a major inflammatory skin disease in which the interaction between IL-17A and epidermal keratinocytes plays a critical pathogenic role. IL-17A stimulates the proliferation of keratinocytes. Keratinocytes also produce a variety of antimicrobial peptides and cytochemokines in response to IL-17A. The antimicrobial peptides further exacerbate skin inflammation. CCL20 produced from IL-17A-stimulated keratinocytes recruits IL-17A-producing Th17 cells and ILC3s and accelerates the feed-forward vicious cycle, which causes fully developed psoriasis. This pathogenetic scheme has been verified with a high clinical efficacy of anti-IL-17A biologics. Therefore, psoriasis is considered an excellent human model of how IL-17A works with target peripheral tissues, and it provides in-depth insight into human autoinflammatory diseases.

References 234

  1. 1.

    Boehncke W.H., Schön M.P. Psoriasis. Lancet. 2015;386:983-994.

    Not in our library10.1016/s0140-6736(14)61909-7

  2. 2.

    Michalek I.M., Loring B., John S.M. A systematic review of worldwide epidemiology of psoriasis. J. Eur. Acad. Dermatol. Venereol. 2017;31:205-212.

    Not in our library10.1111/jdv.13854

  3. 3.

    Ito T., Takahashi H., Kawada A., Iizuka H., Nakagawa H. Epidemiological survey from 2009 to 2012 of psoriatic patients in Japanese Society for Psoriasis Research. J. Dermatol. 2018;45:293-301.

    Not in our library10.1111/1346-8138.14105

  4. 4.

    Ogawa E., Okuyama R., Seki T., Kobayashi A., Oiso N., Muto M., Nakagawa H., Kawada A. Epidemiological survey of patients with psoriasis in Matsumoto city, Nagano Prefecture, Japan. J. Dermatol. 2018;45:314-317.

    Not in our library10.1111/1346-8138.14101

  5. 5.

    Ichiyama S., Ito M., Funasaka Y., Abe M., Nishida E., Muramatsu S., Nishihara H., Kato H., Morita A., Imafuku S., et al. Assessment of medication adherence and treatment satisfaction in Japanese patients with psoriasis of various severities. J. Dermatol. 2018;45:727-731.

    Not in our library10.1111/1346-8138.14225

  6. 6.

    Souza C.S., de Castro C.C.S., Carneiro F.R.O., Pinto J.M.N., Fabricio L.H.Z., Azulay-Abulafia L., Romiti R., Cestari T.F., Suzuki C.E., Biegun P.M., et al. Metabolic syndrome and psoriatic arthritis among patients with psoriasis vulgaris: Quality of life and prevalence. J. Dermatol. 2019;46:3-10.

    Not in our library10.1111/1346-8138.14706

  7. 7.

    Takahashi H., Satoh K., Takagi A., Iizuka H. Cost-efficacy and pharmacoeconomics of psoriatic patients in Japan: Analysis from a single outpatient clinic. J. Dermatol. 2019;46:478-481.

    Not in our library10.1111/1346-8138.14876

  8. 8.

    Miller R.A. The Koebner phenomenon. Int. J. Dermatol. 1982;21:192-197.

    Not in our library10.1111/j.1365-4362.1982.tb02070.x

  9. 9.

    Weiss G., Shemer A., Trau H. The Koebner phenomenon: Review of the literature. J. Eur. Acad. Dermatol. Venereol. 2002;16:241-248.

    Not in our library10.1046/j.1473-2165.2002.00406.x

  10. 10.

    Dai Y.X., Wang S.C., Chou Y.J., Chang Y.T., Chen T.J., Li C.P., Wu C.Y. Smoking, but not alcohol, is associated with risk of psoriasis in a Taiwanese population-based cohort study. J. Am. Acad. Dermatol. 2019;80:727-734.

    Not in our library10.1016/j.jaad.2018.11.015

  11. 11.
    Risk Factors for the Development of Psoriasis · 2019
    No notice
  12. 12.

    O’Rielly D.D., Jani M., Rahman P., Elder J.T. The Genetics of Psoriasis and Psoriatic Arthritis. J. Rheumatol Suppl. 2019;95:46-50.

    Not in our library10.3899/jrheum.190119

  13. 13.

    Elder J.T. Expanded genome-wide association study meta-analysis of psoriasis expands the catalog of common psoriasis-associated variants. J. Investig. Dermatol. Symp. Proc. 2018;19:S77-S78.

    Not in our library10.1016/j.jisp.2018.09.005

  14. 14.

    Diani M., Perego S., Sansoni V., Bertino L., Gomarasca M., Faraldi M., Pigatto P.D.M., Damiani G., Banfi G., Altomare G., et al. Differences in osteoimmunological biomarkers predictive of psoriatic arthritis among a large Italian cohort of psoriatic patients. Int. J. Mol. Sci. 2019;20:5617.

    Not in our library10.3390/ijms20225617

  15. 15.

    Mease P.J., Palmer J.B., Hur P., Strober B.E., Lebwohl M., Karki C., Reed G.W., Etzel C.J., Greenberg J.D., Helliwell P.S. Utilization of the validated psoriasis epidemiology screening tool to identify signs and symptoms of psoriatic arthritis among those with psoriasis: A cross-sectional analysis from the US-based Corrona Psoriasis Registry. J. Eur. Acad. Dermatol. Venereol. 2019;33:886-892.

    Not in our library10.1111/jdv.15443

  16. 16.

    Yamamoto T., Kawada A. Clinical characteristics of Japanese patients with psoriatic arthritis: Comparison with East Asian countries. J. Dermatol. 2018;45:273-278.

    Not in our library10.1111/1346-8138.14097

  17. 17.

    Yamamoto T., Ohtsuki M., Sano S., Morita A., Igarashi A., Okuyama R., Kawada A. Late-onset psoriatic arthritis in Japanese patients. J. Dermatol. 2019;46:169-170.

    Not in our library10.1111/1346-8138.14752

  18. 18.

    Yamamoto T., Ohtsuki M., Sano S., Morita A., Igarashi A., Okuyama R., Kawada A. Switching biologics in the treatment of psoriatic arthritis in Japan. J. Dermatol. 2019;46:e113-e114.

    Not in our library10.1111/1346-8138.14622

  19. 19.

    Umezawa Y., Yanaba K., Asahina A., Nakagawa H., Fukuda T., Fukuda K. Usefulness of dual-energy computed tomography for the evaluation of psoriatic arthritis accompanied by knee osteoarthritis. J. Dermatol. 2019;46:e30-e32.

    Not in our library10.1111/1346-8138.14530

  20. 20.

    Furue K., Ito T., Tsuji G., Kadono T., Nakahara T., Furue M. Autoimmunity and autoimmune co-morbidities in psoriasis. Immunology. 2018;154:21-27.

    Not in our library10.1111/imm.12891

  21. 21.

    Ho Y.H., Hu H.Y., Chang Y.T., Li C.P., Wu C.Y. Psoriasis is associated with increased risk of bullous pemphigoid: A nationwide population-based cohort study in Taiwan. J. Dermatol. 2019;46:604-609.

    Not in our library10.1111/1346-8138.14902

  22. 22.

    Ichiyama S., Hoashi T., Kanda N., Hashimoto H., Matsushita M., Nozawa K., Ueno T., Saeki H. Psoriasis vulgaris associated with systemic lupus erythematosus successfully treated with apremilast. J. Dermatol. 2019;46:e219-e221.

    Not in our library10.1111/1346-8138.14728

  23. 23.

    Chujo S., Asahina A., Itoh Y., Kobayashi K., Sueki H., Ishiji T., Umezawa Y., Nakagawa H. New onset of psoriasis during nivolumab treatment for lung cancer. J. Dermatol. 2018;45:e55-e56.

    Not in our library10.1111/1346-8138.14167

  24. 24.

    Kamata M., Asano Y., Shida R., Maeda N., Yoshizaki A., Miyagaki T., Kawashima T., Tada Y., Sato S. Secukinumab decreased circulating anti-BP180-NC16a autoantibodies in a patient with coexisting psoriasis vulgaris and bullous pemphigoid. J. Dermatol. 2019;46:e216-e217.

    Not in our library10.1111/1346-8138.14760

  25. 25.

    Bayaraa B., Imafuku S. Relationship between environmental factors, age of onset and familial history in Japanese patients with psoriasis. J. Dermatol. 2018;45:715-718.

    Not in our library10.1111/1346-8138.14321

  26. 26.

    Chiu H.Y., Chang W.L., Shiu M.N., Huang W.F., Tsai T.F. Psoriasis is associated with a greater risk for cardiovascular procedure and surgery in patients with hypertension: A nationwide cohort study. J. Dermatol. 2018;45:1381-1388.

    Not in our library10.1111/1346-8138.14654

  27. 27.

    Furue M., Kadono T. “Inflammatory skin march” in atopic dermatitis and psoriasis. Inflamm. Res. 2017;66:833-842.

    Not in our library10.1007/s00011-017-1065-z

  28. 28.

    Momose M., Asahina A., Fukuda T., Sakuma T., Umezawa Y., Nakagawa H. Evaluation of epicardial adipose tissue volume and coronary artery calcification in Japanese patients with psoriasis vulgaris. J. Dermatol. 2018;45:1349-1352.

    Not in our library10.1111/1346-8138.14618

  29. 29.

    Takamura S., Takahashi A., Inoue Y., Teraki Y. Effects of tumor necrosis factor-α, interleukin-23 and interleukin-17A inhibitors on bodyweight and body mass index in patients with psoriasis. J. Dermatol. 2018;45:1130-1134.

    Not in our library10.1111/1346-8138.14526

  30. 30.

    Wang C.C., Tang C.H., Huang K.C., Huang S.Y., Sue Y.M. Increased risk of incident psoriasis in end-stage renal disease patients on chronic hemodialysis: A nationwide population-based cohort study. J. Dermatol. 2018;45:1063-1070.

    Not in our library10.1111/1346-8138.14531

  31. 31.

    Han J.H., Lee J.H., Han K.D., Kim H.N., Bang C.H., Park Y.M., Lee J.Y., Kim T.Y. Increased risk of psoriasis in subjects with abdominal obesity: A nationwide population-based study. J. Dermatol. 2019;46:695-701.

    Not in our library10.1111/1346-8138.14939

  32. 32.

    Jung K.J., Kim T.G., Lee J.W., Lee M., Oh J., Lee S.E., Chang H.J., Jee S.H., Lee M.G. Increased risk of atherosclerotic cardiovascular disease among patients with psoriasis in Korea: A 15-year nationwide population-based cohort study. J. Dermatol. 2019;46:859-866.

    Not in our library10.1111/1346-8138.15052

  33. 33.

    Masaki S., Bayaraa B., Imafuku S. Prevalence of inflammatory bowel disease in Japanese psoriatic patients. J. Dermatol. 2019;46:590-594.

    Not in our library10.1111/1346-8138.14900

  34. 34.

    Tokuyama M., Shimizu T., Yamada T., Kondoh A., Mabuchi T. Case of psoriasis vulgaris with atrial fibrillation, heart failure and chronic kidney disease which were found accidentally through blood examination during apremilast treatment. J. Dermatol. 2019;46:e239-e240.

    Not in our library10.1111/1346-8138.14784

  35. 35.

    Yamazaki F., Takehana K., Tamashima M., Okamoto H. Improvement in abnormal coronary arteries estimated by coronary computed tomography angiography after secukinumab treatment in a Japanese psoriatic patient. J. Dermatol. 2019;46:e51-e52.

    Not in our library10.1111/1346-8138.14545

  36. 36.

    Wójcik P., Biernacki M., Wroński A., Łuczaj W., Waeg G., Žarković N., Skrzydlewska E. Altered lipid metabolism in blood mononuclear cells of psoriatic patients indicates differential changes in psoriasis vulgaris and psoriatic arthritis. Int. J. Mol. Sci. 2019;20:4249.

    Not in our library10.3390/ijms20174249

  37. 37.

    Lee J.H., Kim H.J., Han K.D., Kim H.N., Park Y.M., Lee J.Y., Park Y.G., Lee Y.B. Cancer risk in 892089 patients with psoriasis in Korea: A nationwide population-based cohort study. J. Dermatol. 2019;46:95-102.

    Not in our library10.1111/1346-8138.14698

  38. 38.

    Hsu S., Papp K.A., Lebwohl M.G., Bagel J., Blauvelt A., Duffin K.C., Crowley J., Eichenfield L.F., Feldman S.R., Fiorentino D.F., et al. Consensus guidelines for the management of plaque psoriasis. Arch. Dermatol. 2012;148:95-102.

    Not in our library10.1001/archdermatol.2011.1410

  39. 39.

    Imafuku S., Zheng M., Tada Y., Zhang X., Theng C., Thevarajah S., Zhao Y., Song H.J. Asian consensus on assessment and management of mild to moderate plaque psoriasis with topical therapy. J. Dermatol. 2018;45:805-811.

    Not in our library10.1111/1346-8138.14338

  40. 40.

    Meephansan J., Subpayasarn U., Ponnikorn S., Chakkavittumrong P., Juntongjin P., Komine M., Ohtsuki M., Poovorawan Y. Methotrexate, but not narrowband ultraviolet B radiation, suppresses interleukin-33 mRNA levels in psoriatic plaques and protein levels in serum of patients with psoriasis. J. Dermatol. 2018;45:322-325.

    Not in our library10.1111/1346-8138.14009

  41. 41.

    Kishimoto M., Komine M., Hioki T., Kamiya K., Sugai J., Ohtsuki M. Real-world use of apremilast for patients with psoriasis in Japan. J. Dermatol. 2018;45:1345-1348.

    Not in our library10.1111/1346-8138.14617

  42. 42.

    Morita A. Current developments in phototherapy for psoriasis. J. Dermatol. 2018;45:287-292.

    Not in our library10.1111/1346-8138.14213

  43. 43.

    Oh E.H., Koh W.S., Shin J.M., Kim J.E., Ko J.Y., Ro Y.S. Clinical experience of cyclosporin treatment in patients with psoriasis and psoriatic arthritis. J. Dermatol. 2018;45:329-330.

    Not in our library10.1111/1346-8138.13746

  44. 44.

    Pongparit K., Chularojanamontri L., Limphoka P., Silpa-Archa N., Wongpraparat C. Effectiveness of and factors associated with clinical response to methotrexate under daily life conditions in Asian patients with psoriasis: A retrospective cohort study. J. Dermatol. 2018;45:540-545.

    Not in our library10.1111/1346-8138.14270

  45. 45.

    Okazaki S., Osawa R., Nakajima H., Nakajima K., Sano S. Favorable response to apremilast in a patient with refractory psoriasis verrucosa. J. Dermatol. 2019;46:544-547.

    Not in our library10.1111/1346-8138.14877

  46. 46.

    Furue K., Ito T., Furue M. Differential efficacy of biologic treatments targeting the TNF-α/IL-23/IL-17 axis in psoriasis and psoriatic arthritis. Cytokine. 2018;111:182-188.

    Not in our library10.1016/j.cyto.2018.08.025

  47. 47.

    Furue K., Ito T., Tsuji G., Kadono T., Furue M. Psoriasis and the TNF/IL23/IL17 axis. G. Ital. Dermatol. Venereol. 2019;154:418-424.

    Not in our library10.23736/s0392-0488.18.06202-8

  48. 48.
    Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response · 2019
    No notice
  49. 49.

    Kamata M., Tada Y. Safety of biologics in psoriasis. J. Dermatol. 2018;45:279-286.

    Not in our library10.1111/1346-8138.14096

  50. 50.

    Momose M., Asahina A., Umezawa Y., Nakagawa H. Long-term clinical efficacy and safety of secukinumab for Japanese patients with psoriasis: A single-center experience. J. Dermatol. 2018;45:318-321.

    Not in our library10.1111/1346-8138.14145

  51. 51.

    Ogawa E., Sato Y., Minagawa A., Okuyama R. Pathogenesis of psoriasis and development of treatment. J. Dermatol. 2018;45:264-272.

    Not in our library10.1111/1346-8138.14139

  52. 52.

    Ohtsuki M., Kubo H., Morishima H., Goto R., Zheng R., Nakagawa H. Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study. J. Dermatol. 2018;45:1053-1062.

    Not in our library10.1111/1346-8138.14504

  53. 53.

    Bayaraa B., Imafuku S. Sustainability and switching of biologics for psoriasis and psoriatic arthritis at Fukuoka University Psoriasis Registry. J. Dermatol. 2019;46:389-398.

    Not in our library10.1111/1346-8138.14834

  54. 54.

    Kamiya K., Karakawa M., Komine M., Kishimoto M., Sugai J., Ohtsuki M. Results of a retrospective study on the efficacy and safety of adalimumab 80 mg administrated every other week in patients with psoriasis at a single Japanese institution. J. Dermatol. 2019;46:199-205.

    Not in our library10.1111/1346-8138.14782

  55. 55.

    Komatsu-Fujii T., Honda T., Otsuka A., Kabashima K. Inverse responses of the skin and nail lesions of psoriatic arthritis to an anti-interleukin-17A antibody and an anti-tumor necrosis factor-α antibody. J. Dermatol. 2019;46:e440-e441.

    Not in our library10.1111/1346-8138.15006

  56. 56.

    Komatsu-Fujii T., Honda T., Otsuka A., Kabashima K. Improvement of nail lesions in a patient with psoriatic arthritis by switching the treatment from an anti-interleukin-17A antibody to an anti-tumor necrosis factor-α antibody. J. Dermatol. 2019;46:e158-e160.

    Not in our library10.1111/1346-8138.14700

  57. 57.

    Lee M.G., Huang Y.H., Lee J.H., Lee S.C., Kim T.G., Aw D.C., Bao W., Dee C.M.A., Guana A., Tsai T.F. Secukinumab demonstrates superior efficacy and a faster response in clearing skin in Asian subjects with moderate to severe plaque psoriasis compared with ustekinumab: Subgroup analysis from the CLEAR study. J. Dermatol. 2019;46:752-758.

    Not in our library10.1111/1346-8138.15004

  58. 58.

    Okubo Y., Ohtsuki M., Morita A., Yamaguchi M., Shima T., Tani Y., Nakagawa H. Long-term efficacy and safety of secukinumab in Japanese patients with moderate to severe plaque psoriasis: 3-year results of a double-blind extension study. J. Dermatol. 2019;46:186-192.

    Not in our library10.1111/1346-8138.14761

  59. 59.

    Shibata T., Muto J., Takama H., Yanagishita T., Ito T., Watanabe D. Case of psoriatic erythroderma induced by the discontinuation of the chronic use of topical steroid after dialysis initiation and successfully treated with secukinumab. J. Dermatol. 2019;46:e119-e120.

    Not in our library10.1111/1346-8138.14649

  60. 60.

    Tada Y., Ishii K., Kimura J., Hanada K., Kawaguchi I. Patient preference for biologic treatments of psoriasis in Japan. J. Dermatol. 2019;46:466-477.

    Not in our library10.1111/1346-8138.14870

  61. 61.

    Tsuruta N., Narisawa Y., Imafuku S., Ito K., Yamaguchi K., Miyagi T., Takahashi K., Fukamatsu H., Morizane S., Koketsu H., et al. Cross-sectional multicenter observational study of psoriatic arthritis in Japanese patients: Relationship between skin and joint symptoms and results of treatment with tumor necrosis factor-α inhibitors. J. Dermatol. 2019;46:193-198.

    Not in our library10.1111/1346-8138.14745

  62. 62.

    Veale D.J., Fearon U. The pathogenesis of psoriatic arthritis. Lancet. 2018;391:2273-2284.

    Not in our library10.1016/s0140-6736(18)30830-4

  63. 63.

    Assefa G.T., Kaneko S., Oguro H., Morita E. Treatment of psoriasis and psoriatic arthritis with secukinumab after unsatisfactory response to ustekinumab in multiple sclerosis patient. J. Dermatol. 2019;46:e112-e113.

    Not in our library10.1111/1346-8138.14619

  64. 64.

    Mourad A., Gniadecki R. Treatment of dactylitis and enthesitis in psoriatic arthritis with biologic agents: A systematic review and metaanalysis. J. Rheumatol. 2019;47:59-65.

    Not in our library10.3899/jrheum.180797

  65. 65.

    Korman N.J. Management of psoriasis as a systemic disease: What is the evidence? Br. J. Dermatol. 2019.

    Not in our library10.1111/bjd.18245

  66. 66.

    Lockshin B., Balagula Y., Merola J.F. Interleukin 17, inflammation, and cardiovascular risk in patients with psoriasis. J. Am. Acad. Dermatol. 2018;79:345-352.

    Not in our library10.1016/j.jaad.2018.02.040

  67. 67.

    Erichsen C.Y., Jensen P., Kofoed K. Biologic therapies targeting the interleukin (IL)-23/IL-17 immune axis for the treatment of moderate-to-severe plaque psoriasis: A systematic review and meta-analysis. J. Eur. Acad. Dermatol. Venereol. 2020;34:30-38.

    Not in our library10.1111/jdv.15879

  68. 68.

    Krueger J.G., Brunner P.M. Interleukin-17 alters the biology of many cell types involved in the genesis of psoriasis, systemic inflammation and associated comorbidities. Exp. Dermatol. 2018;27:115-123.

    Not in our library10.1111/exd.13467

  69. 69.

    Krueger J.G., Wharton K.A., Schlitt T., Suprun M., Torene R.I., Jiang X., Wang C.Q., Fuentes-Duculan J., Hartmann N., Peters T., et al. IL-17A inhibition by secukinumab induces early clinical, histopathologic, and molecular resolution of psoriasis. J. Allergy Clin. Immunol. 2019;144:750-763.

    Not in our library10.1016/j.jaci.2019.04.029

  70. 70.

    Mease P.J., Smolen J.S., Behrens F., Nash P., Liu Leage S., Li L., Tahir H., Gooderham M., Krishnan E., Liu-Seifert H., et al. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial. Ann. Rheum. Dis. 2020;79:123-131.

    Not in our library10.1136/annrheumdis-2019-215386

  71. 71.

    Warren R.B., Barker J., Finlay A.Y., Burden A.D., Kirby B., Armendariz Y., Williams R., Hatchard C., Khare S., Griffiths C.E.M. Secukinumab for patients failing previous TNFα-inhibitor therapy: Results of a randomised open-label study (Signature). Br. J. Dermatol. 2019.

    Not in our library10.1111/bjd.18623

  72. 72.

    Hawkes J.E., Chan T.C., Krueger J.G. Psoriasis pathogenesis and the development of novel targeted immune therapies. J. Allergy Clin. Immunol. 2017;140:645-653.

    Not in our library10.1016/j.jaci.2017.07.004

  73. 73.

    Hawkes J.E., Yan B.Y., Chan T.C., Krueger J.G. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. J. Immunol. 2018;201:1605-1613.

    Not in our library10.4049/jimmunol.1800013

  74. 74.

    Langrish C.L., Chen Y., Blumenschein W.M., Mattson J., Basham B., Sedgwick J.D., McClanahan T., Kastelein R.A., Cua D.J. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 2005;201:233-240.

    Not in our library10.1084/jem.20041257

  75. 75.

    Shiga T., Sato K., Kataoka S., Sano S. TNF inhibitors directly target Th17 cells via attenuation of autonomous TNF/TNFR2 signalling in psoriasis. J. Dermatol. Sci. 2015;77:79-81.

    Not in our library10.1016/j.jdermsci.2014.11.008

  76. 76.

    Schüler R., Brand A., Klebow S., Wild J., Veras F.P., Ullmann E., Roohani S., Kolbinger F., Kossmann S., Wohn C., et al. Antagonization of IL-17A attenuates skin inflammation and vascular dysfunction in mouse models of psoriasis. J. Investig. Dermatol. 2019;139:638-647.

    Not in our library10.1016/j.jid.2018.09.021

  77. 77.

    Moos S., Mohebiany A.N., Waisman A., Kurschus F.C. Imiquimod-induced psoriasis in mice depends on the IL-17 signaling of keratinocytes. J. Investig. Dermatol. 2019;139:1110-1117.

    Not in our library10.1016/j.jid.2019.01.006

  78. 78.

    Mabuchi T., Takekoshi T., Hwang S.T. Epidermal CCR6+ γδ T cells are major producers of IL-22 and IL-17 in a murine model of psoriasiform dermatitis. J. Immunol. 2011;187:5026-5031.

    Not in our library10.4049/jimmunol.1101817

  79. 79.

    Mabuchi T., Singh T.P., Takekoshi T., Jia G.F., Wu X., Kao M.C., Weiss I., Farber J.M., Hwang S.T. CCR6 is required for epidermal trafficking of γδ-T cells in an IL-23-induced model of psoriasiform dermatitis. J. Investig. Dermatol. 2013;133:164-171.

    Not in our library10.1038/jid.2012.260

  80. 80.

    Nakajima K., Sano S. Mouse models of psoriasis and their relevance. J. Dermatol. 2018;45:252-263.

    Not in our library10.1111/1346-8138.14112

  81. 81.
    The IL-17 Family of Cytokines in Psoriasis: IL-17A and Beyond · 2018
    No notice
  82. 82.

    McGeachy M.J., Cua D.J., Gaffen S.L. The IL-17 family of cytokines in health and disease. Immunity. 2019;50:892-906.

    Not in our library10.1016/j.immuni.2019.03.021

  83. 83.

    Buckley K.M., Ho E.C.H., Hibino T., Schrankel C.S., Schuh N.W., Wang G., Rast J.P. IL17 factors are early regulators in the gut epithelium during inflammatory response to Vibrio in the sea urchin larva. Elife. 2017;6.

    Not in our library10.7554/elife.23481

  84. 84.

    Han Q., Das S., Hirano M., Holland S.J., McCurley N., Guo P., Rosenberg C.S., Boehm T., Cooper M.D. Characterization of lamprey IL-17 family members and their receptors. J. Immunol. 2015;195:5440-5451.

    Not in our library10.4049/jimmunol.1500892

  85. 85.

    Aktar M.K., Kido-Nakahara M., Furue M., Nakahara T. Mutual upregulation of endothelin-1 and IL-25 in atopic dermatitis. Allergy. 2015;70:846-854.

    Not in our library10.1111/all.12633

  86. 86.

    Cua D.J., Tato C.M. Innate IL-17-producing cells: The sentinels of the immune system. Nat. Rev. Immunol. 2010;10:479-489.

    Not in our library10.1038/nri2800

  87. 87.

    Chen L., He Z., Slinger E., Bongers G., Lapenda T.L.S., Pacer M.E., Jiao J., Beltrao M.F., Soto A.J., Harpaz N., et al. IL-23 activates innate lymphoid cells to promote neonatal intestinal pathology. Mucosal Immunol. 2015;8:390-402.

    Not in our library10.1038/mi.2014.77

  88. 88.

    Cai Y., Shen X., Ding C., Qi C., Li K., Li X., Jala V.R., Zhang H.G., Wang T., Zheng J., et al. Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation. Immunity. 2011;35:596-610.

    Not in our library10.1016/j.immuni.2011.08.001

  89. 89.

    Villanova F., Flutter B., Tosi I., Grys K., Sreeneebus H., Perera G.K., Chapman A., Smith C.H., Di Meglio P., Nestle F.O. Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis. J. Investig. Dermatol. 2014;134:984-991.

    Not in our library10.1038/jid.2013.477

  90. 90.

    Matsuzaki G., Umemura M. Interleukin-17 family cytokines in protective immunity against infections: Role of hematopoietic cell-derived and non-hematopoietic cell-derived interleukin-17s. Microbiol. Immunol. 2018;62:1-13.

    Not in our library10.1111/1348-0421.12560

  91. 91.

    Chang S.H., Reynolds J.M., Pappu B.P., Chen G., Martinez G.J., Dong C. Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E. Immunity. 2011;35:611-621.

    Not in our library10.1016/j.immuni.2011.09.010

  92. 92.

    Hu Y., Ota N., Peng I., Refino C.J., Danilenko D.M., Caplazi P., Ouyang W. IL-17RC is required for IL-17A- and IL-17F-dependent signaling and the pathogenesis of experimental autoimmune encephalomyelitis. J. Immunol. 2010;184:4307-4316.

    Not in our library10.4049/jimmunol.0903614

  93. 93.

    Su Y., Huang J., Zhao X., Lu H., Wang W., Yang X.O., Shi Y., Wang X., Lai Y., Dong C. Interleukin-17 receptor D constitutes an alternative receptor for interleukin-17A important in psoriasis-like skin inflammation. Sci. Immunol. 2019;4.

    Not in our library10.1126/sciimmunol.aau9657

  94. 94.

    Liu C., Swaidani S., Qian W., Kang Z., Sun P., Han Y., Wang C., Gulen M.F., Yin W., Zhang C., et al. A CC’ loop decoy peptide blocks the interaction between Act1 and IL-17RA to attenuate IL-17- and IL-25-induced inflammation. Sci.Signal. 2011;4:ra72.

    Not in our library10.1126/scisignal.2001843

  95. 95.

    Sønder S.U., Saret S., Tang W., Sturdevant D.E., Porcella S.F., Siebenlist U. IL-17-induced NF-kappaB activation via CIKS/Act1: Physiologic significance and signaling mechanisms. J. Biol. Chem. 2011;286:12881-12890.

    Not in our library10.1074/jbc.m110.199547

  96. 96.

    Okada S., Puel A., Casanova J.L., Kobayashi M. Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity. Clin. Transl. Immunology. 2016;5:e114.

    Not in our library10.1038/cti.2016.71

  97. 97.

    Wang M., Zhang S., Zheng G., Huang J., Songyang Z., Zhao X., Lin X. Gain-of-function mutation of Card14 leads to spontaneous psoriasis-like skin inflammation through enhanced keratinocyte response to IL-17A. Immunity. 2018;49:66-79.

    Not in our library10.1016/j.immuni.2018.05.012

  98. 98.

    Chen X., Cai G., Liu C., Zhao J., Gu C., Wu L., Hamilton T.A., Zhang C.J., Ko J., Zhu L., et al. IL-17R-EGFR axis links wound healing to tumorigenesis in Lrig1(+) stem cells. J. Exp. Med. 2019;216:195-214.

    Not in our library10.1084/jem.20171849

  99. 99.

    Tsang M., Friesel R., Kudoh T., Dawid I.B. Identification of Sef, a novel modulator of FGF signalling. Nat. Cell Biol. 2002;4:165-169.

    Not in our library10.1038/ncb749

  100. 100.
    Psoriasis: A STAT3-Centric View · 2018
    No notice
  101. 101.

    Sano S., Chan K.S., Carbajal S., Clifford J., Peavey M., Kiguchi K., Itami S., Nickoloff B.J., DiGiovanni J. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat. Med. 2005;11:43-49.

    Not in our library10.1038/nm1162

  102. 102.

    Miyoshi K., Takaishi M., Nakajima K., Ikeda M., Kanda T., Tarutani M., Iiyama T., Asao N., DiGiovanni J., Sano S. Stat3 as a therapeutic target for the treatment of psoriasis: A clinical feasibility study with STA-21, a Stat3 inhibitor. J. Investig. Dermatol. 2011;131:108-117.

    Not in our library10.1038/jid.2010.255

  103. 103.

    Bae H.C., Jeong S.H., Kim J.H., Lee H., Ryu W.I., Kim M.G., Son E.D., Lee T.R., Son S.W. RIP4 upregulates CCL20 expression through STAT3 signalling in cultured keratinocytes. Exp. Dermatol. 2018;27:1126-1133.

    Not in our library10.1111/exd.13750

  104. 104.

    Shi X., Jin L., Dang E., Chang T., Feng Z., Liu Y., Wang G. IL-17A upregulates keratin 17 expression in keratinocytes through STAT1- and STAT3-dependent mechanisms. J. Investig. Dermatol. 2011;131:2401-2408.

    Not in our library10.1038/jid.2011.222

  105. 105.

    Honma M., Minami-Hori M., Takahashi H., Iizuka H. Podoplanin expression in wound and hyperproliferative psoriatic epidermis: Regulation by TGF-β and STAT-3 activating cytokines, IFN-γ, IL-6, and IL-22. J. Dermatol. Sci. 2012;65:134-140.

    Not in our library10.1016/j.jdermsci.2011.11.011

  106. 106.

    Miyoshi K., Takaishi M., Digiovanni J., Sano S. Attenuation of psoriasis-like skin lesion in a mouse model by topical treatment with indirubin and its derivastive E804. J. Dermatol. Sci. 2012;65:70-72.

    Not in our library10.1016/j.jdermsci.2011.10.001

  107. 107.

    Ekman A.K., Bivik Eding C., Rundquist I., Enerbäck C. IL-17 and IL-22 promote keratinocyte stemness in the germinative compartment in psoriasis. J. Investig. Dermatol. 2019;139:1564-1573.

    Not in our library10.1016/j.jid.2019.01.014

  108. 108.

    Karbach S., Croxford A.L., Oelze M., Schüler R., Minwegen D., Wegner J., Koukes L., Yogev N., Nikolaev A., Reißig S., et al. Interleukin 17 drives vascular inflammation, endothelial dysfunction, and arterial hypertension in psoriasis-like skin disease. Arterioscler. Thromb. Vasc. Biol. 2014;34:2658-2668.

    Not in our library10.1161/atvbaha.114.304108

  109. 109.

    Cordoro K.M., Hitraya-Low M., Taravati K., Sandoval P.M., Kim E., Sugarman J., Pauli M.L., Liao W., Rosenblum M.D. Skin-infiltrating, interleukin-22-producing T cells differentiate pediatric psoriasis from adult psoriasis. J. Am. Acad. Dermatol. 2017;77:417-424.

    Not in our library10.1016/j.jaad.2017.05.017

  110. 110.

    Diani M., Altomare G., Reali E. T cell responses in psoriasis and psoriatic arthritis. Autoimmun. Rev. 2015;14:286-292.

    Not in our library10.1016/j.autrev.2014.11.012

  111. 111.

    Puel A., Cypowyj S., Bustamante J., Wright J.F., Liu L., Lim H.K., Migaud M., Israel L., Chrabieh M., Audry M., et al. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science. 2011;332:65-68.

    Not in our library10.1126/science.1200439

  112. 112.

    Boisson B., Wang C., Pedergnana V., Wu L., Cypowyj S., Rybojad M., Belkadi A., Picard C., Abel L., Fieschi C., et al. An ACT1 mutation selectively abolishes interleukin-17 responses in humans with chronic mucocutaneous candidiasis. Immunity. 2013;39:676-686.

    Not in our library10.1016/j.immuni.2013.09.002

  113. 113.

    Ling Y., Cypowyj S., Aytekin C., Galicchio M., Camcioglu Y., Nepesov S., Ikinciogullari A., Dogu F., Belkadi A., Levy R., et al. Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis. J. Exp. Med. 2015;212:619-631.

    Not in our library10.1084/jem.20141065

  114. 114.

    Ferreira M.C., Whibley N., Mamo A.J., Siebenlist U., Chan Y.R., Gaffen S.L. Interleukin-17-induced protein lipocalin 2 is dispensable for immunity to oral candidiasis. Infect. Immun. 2014;82:1030-1035.

    Not in our library10.1128/iai.01389-13

  115. 115.

    Conti H.R., Shen F., Nayyar N., Stocum E., Sun J.N., Lindemann M.J., Ho A.W., Hai J.H., Yu J.J., Jung J.W., et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J. Exp. Med. 2009;206:299-311.

    Not in our library10.1084/jem.20081463

  116. 116.

    Conti H.R., Gaffen S.L. IL-17-mediated immunity to the opportunistic fungal pathogen Candida albicans. J. Immunol. 2015;195:780-788.

    Not in our library10.4049/jimmunol.1500909

  117. 117.

    Li J., Vinh D.C., Casanova J.L., Puel A. Inborn errors of immunity underlying fungal diseases in otherwise healthy individuals. Curr. Opin. Microbiol. 2017;40:46-57.

    Not in our library10.1016/j.mib.2017.10.016

  118. 118.

    Sparber F., De Gregorio C., Steckholzer S., Ferreira F.M., Dolowschiak T., Ruchti F., Kirchner F.R., Mertens S., Prinz I., Joller N., et al. The skin commensal yeast Malassezia triggers a type 17 response that coordinates anti-fungal immunity and exacerbates skin inflammation. Cell Host Microbe. 2019;25:389-403.

    Not in our library10.1016/j.chom.2019.02.002

  119. 119.

    Wohn C., Brand A., van Ettinger K., Brouwers-Haspels I., Waisman A., Laman J.D., Clausen B.E. Gradual development of psoriatic skin lesions by constitutive low-level expression of IL-17A. Cell. Immunol. 2016;308:57-65.

    Not in our library10.1016/j.cellimm.2015.11.006

  120. 120.

    Aggarwal S., Ghilardi N., Xie M.H., de Sauvage F.J., Gurney A.L. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J. Biol. Chem. 2003;278:1910-1914.

    Not in our library10.1074/jbc.m207577200

  121. 121.

    Ivanov I.I., McKenzie B.S., Zhou L., Tadokoro C.E., Lepelley A., Lafaille J.J., Cua D.J., Littman D.R. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121-1133.

    Not in our library10.1016/j.cell.2006.07.035

  122. 122.

    Gaffen S.L. Structure and signalling in the IL-17 receptor family. Nat. Rev. Immunol. 2009;9:556-567.

    Not in our library10.1038/nri2586

  123. 123.

    Villegas J.A., Bayer A.C., Ider K., Bismuth J., Truffault F., Roussin R., Santelmo N., Le Panse R., Berrih-Aknin S., Dragin N. Il-23/Th17 cell pathway: A promising target to alleviate thymic inflammation maintenance in myasthenia gravis. J. Autoimmun. 2019;98:59-73.

    Not in our library10.1016/j.jaut.2018.11.005

  124. 124.

    Chan J.R., Blumenschein W., Murphy E., Diveu C., Wiekowski M., Abbondanzo S., Lucian L., Geissler R., Brodie S., Kimball A.B., et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J. Exp. Med. 2006;203:2577-2587.

    Not in our library10.1084/jem.20060244

  125. 125.

    Furue M., Kadono T. The contribution of IL-17 to the development of autoimmunity in psoriasis. Innate Immun. 2019;25:337-343.

    Not in our library10.1177/1753425919852156

  126. 126.

    Arakawa A., Siewert K., Stöhr J., Besgen P., Kim S.M., Rühl G., Nickel J., Vollmer S., Thomas P., Krebs S., et al. Melanocyte antigen triggers autoimmunity in human psoriasis. J. Exp. Med. 2015;212:2203-2212.

    Not in our library10.1084/jem.20151093

  127. 127.

    Lee E., Trepicchio W.L., Oestreicher J.L., Pittman D., Wang F., Chamian F., Dhodapkar M., Krueger J.G. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J. Exp. Med. 2004;199:125-130.

    Not in our library10.1084/jem.20030451

  128. 128.

    Zaba L.C., Cardinale I., Gilleaudeau P., Sullivan-Whalen M., Suárez-Fariñas M., Fuentes-Duculan J., Novitskaya I., Khatcherian A., Bluth M.J., Lowes M.A., et al. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J. Exp. Med. 2007;204:3183-3194.

    Not in our library10.1084/jem.20071094

  129. 129.

    Piskin G., Sylva-Steenland R.M., Bos J.D., Teunissen M.B. In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: Enhanced expression in psoriatic skin. J. Immunol. 2006;176:1908-1915.

    Not in our library10.4049/jimmunol.176.3.1908

  130. 130.
    Epigenetic control of IL-23 expression in keratinocytes is important for chronic skin inflammation · 2018
    No notice
  131. 131.

    Tu Z., Zhang S., Zhou G., Zhou L., Xiang Q., Chen Q., Zhao P., Zhan H., Zhou H., Sun L. LMO4 is a disease-provocative transcription coregulator activated by IL-23 in psoriatic keratinocytes. J. Investig. Dermatol. 2018;138:1078-1087.

    Not in our library10.1016/j.jid.2017.12.010

  132. 132.

    McInnes I.B., Kavanaugh A., Gottlieb A.B., Puig L., Rahman P., Ritchlin C., Brodmerkel C., Li S., Wang Y., Mendelsohn A.M., et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet. 2013;382:780-789.

    Not in our library10.1016/s0140-6736(13)60594-2

  133. 133.

    Papp K.A., Blauvelt A., Bukhalo M., Gooderham M., Krueger J.G., Lacour J.P., Menter A., Philipp S., Sofen H., Tyring S., et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N. Engl. J. Med. 2017;376:1551-1560.

    Not in our library10.1056/nejmoa1607017

  134. 134.

    Blauvelt A., Papp K.A., Griffiths C.E., Randazzo B., Wasfi Y., Shen Y.K., Li S., Kimball A.B. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J. Am. Acad. Dermatol. 2017;76:405-417.

    Not in our library10.1016/j.jaad.2016.11.041

  135. 135.

    Reich K., Papp K.A., Blauvelt A., Tyring S.K., Sinclair R., Thaçi D., Nograles K., Mehta A., Cichanowitz N., Li Q., et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): Results from two randomised controlled, phase 3 trials. Lancet. 2017;390:276-288.

    Not in our library10.1016/s0140-6736(17)31279-5

  136. 136.

    Johansen C., Usher P.A., Kellerup R.B., Lundsgaard D., Iversen L., Kragballe K. Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Br. J. Dermatol. 2009;160:319-324.

    Not in our library10.1111/j.1365-2133.2008.08902.x

  137. 137.

    Johnston A., Fritz Y., Dawes S.M., Diaconu D., Al-Attar P.M., Guzman A.M., Chen C.S., Fu W., Gudjonsson J.E., McCormick T.S., et al. Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation. J. Immunol. 2013;190:2252-2262.

    Not in our library10.4049/jimmunol.1201505

  138. 138.

    Martin D.A., Towne J.E., Kricorian G., Klekotka P., Gudjonsson J.E., Krueger J.G., Russell C.B. The emerging role of IL-17 in the pathogenesis of psoriasis: Preclinical and clinical findings. J. Investig. Dermatol. 2013;133:17-26.

    Not in our library10.1038/jid.2012.194

  139. 139.

    Ramirez-Carrozzi V., Sambandam A., Luis E., Lin Z., Jeet S., Lesch J., Hackney J., Kim J., Zhou M., Lai J., et al. IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. Nat. Immunol. 2011;12:1159-1166.

    Not in our library10.1038/ni.2156

  140. 140.

    Vandeghinste N., Klattig J., Jagerschmidt C., Lavazais S., Marsais F., Haas J.D., Auberval M., Lauffer F., Moran T., Ongenaert M., et al. Neutralization of IL-17C reduces skin inflammation in mouse models of psoriasis and atopic dermatitis. J. Investig. Dermatol. 2018;138:1555-1563.

    Not in our library10.1016/j.jid.2018.01.036

  141. 141.

    Guttman-Yassky E., Krueger J.G. IL-17C: A unique epithelial cytokine with potential for targeting across the spectrum of atopic dermatitis and psoriasis. J. Investig. Dermatol. 2018;138:1467-1469.

    Not in our library10.1016/j.jid.2018.02.037

  142. 142.

    Tsoi L.C., Rodriguez E., Degenhardt F., Baurecht H., Wehkamp U., Volks N., Szymczak S., Swindell W.R., Sarkar M.K., Raja K., et al. Atopic dermatitis is an IL-13-dominant disease with greater molecular heterogeneity compared to psoriasis. J. Investig. Dermatol. 2019;139:1480-1489.

    Not in our library10.1016/j.jid.2018.12.018

  143. 143.

    Pène J., Chevalier S., Preisser L., Vénéreau E., Guilleux M.H., Ghannam S., Molès J.P., Danger Y., Ravon E., Lesaux S., et al. Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J. Immunol. 2008;180:7423-7430.

    Not in our library10.4049/jimmunol.180.11.7423

  144. 144.

    Lande R., Botti E., Jandus C., Dojcinovic D., Fanelli G., Conrad C., Chamilos G., Feldmeyer L., Marinari B., Chon S., et al. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat. Commun. 2014;5:5621.

    Not in our library10.1038/ncomms6621

  145. 145.

    Fuentes-Duculan J., Bonifacio K.M., Hawkes J.E., Kunjravia N., Cueto I., Li X., Gonzalez J., Garcet S., Krueger J.G. Autoantigens ADAMTSL5 and LL37 are significantly upregulated in active Psoriasis and localized with keratinocytes, dendritic cells and other leukocytes. Exp. Dermatol. 2017;26:1075-1082.

    Not in our library10.1111/exd.13378

  146. 146.

    Yunusbaeva M., Valiev R., Bilalov F., Sultanova Z., Sharipova L., Yunusbayev B. Psoriasis patients demonstrate HLA-Cw*06:02 allele dosage-dependent T cell proliferation when treated with hair follicle-derived keratin 17 protein. Sci. Rep. 2018;8:6098.

    Not in our library10.1038/s41598-018-24491-z

  147. 147.

    Cheung K.L., Jarrett R., Subramaniam S., Salimi M., Gutowska-Owsiak D., Chen Y.L., Hardman C., Xue L., Cerundolo V., Ogg G. Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a. J. Exp. Med. 2016;213:2399-2412.

    Not in our library10.1084/jem.20160258

  148. 148.

    Chiricozzi A., Suárez-Fariñas M., Fuentes-Duculan J., Cueto I., Li K., Tian S., Brodmerkel C., Krueger J.G. Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris. Br. J. Dermatol. 2016;174:136-145.

    Not in our library10.1111/bjd.14034

  149. 149.

    Weisman S., Pollack C.R., Gottschalk R.W. Psoriasis disease severity measures: Comparing efficacy of treatments for severe psoriasis. J. Dermatolog. Treat. 2003;14:158-165.

    Not in our library10.1080/09546630310013360

  150. 150.

    Langley R.G., Elewski B.E., Lebwohl M., Reich K., Griffiths C.E., Papp K., Puig L., Nakagawa H., Spelman L., Sigurgeirsson B., et al. Secukinumab in plaque psoriasis--results of two phase 3 trials. N. Engl. J. Med. 2014;371:326-338.

    Not in our library10.1056/nejmoa1314258

  151. 151.

    Gordon K.B., Blauvelt A., Papp K.A., Langley R.G., Luger T., Ohtsuki M., Reich K., Amato D., Ball S.G., Braun D.K., et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N. Engl. J. Med. 2016;375:345-356.

    Not in our library10.1056/nejmoa1512711

  152. 152.

    Lebwohl M., Strober B., Menter A., Gordon K., Weglowska J., Puig L., Papp K., Spelman L., Toth D., Kerdel F., et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N. Engl. J. Med. 2015;373:1318-1328.

    Not in our library10.1056/nejmoa1503824

  153. 153.

    Paramio J.M., Casanova M.L., Segrelles C., Mittnacht S., Lane E.B., Jorcano J.L. Modulation of cell proliferation by cytokeratins K10 and K16. Mol. Cell Biol. 1999;19:3086-3094.

    Not in our library10.1128/mcb.19.4.3086

  154. 154.

    Krueger J.G., Ferris L.K., Menter A., Wagner F., White A., Visvanathan S., Lalovic B., Aslanyan S., Wang E.E., Hall D., et al. Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J. Allergy Clin. Immunol. 2015;136:116-124.

    Not in our library10.1016/j.jaci.2015.01.018

  155. 155.

    Kulke R., Tödt-Pingel I., Rademacher D., Röwert J., Schröder J.M., Christophers E. Co-localized overexpression of GRO-alpha and IL-8 mRNA is restricted to the suprapapillary layers of psoriatic lesions. J. Investig. Dermatol. 1996;106:526-530.

    Not in our library10.1111/1523-1747.ep12343916

  156. 156.

    Furue K., Yamamura K., Tsuji G., Mitoma C., Uchi H., Nakahara T., Kido-Nakahara M., Kadono T., Furue M. Highlighting interleukin-36 signalling in plaque psoriasis and pustular psoriasis. Acta Derm. Venereol. 2018;98:5-13.

    Not in our library10.2340/00015555-2808

  157. 157.

    Johnston A., Xing X., Guzman A.M., Riblett M., Loyd C.M., Ward N.L., Wohn C., Prens E.P., Wang F., Maier L.E., et al. IL-1F5, -F6, -F8, and -F9: A novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression. J. Immunol. 2011;186:2613-2622.

    Not in our library10.4049/jimmunol.1003162

  158. 158.

    Homey B., Dieu-Nosjean M.C., Wiesenborn A., Massacrier C., Pin J.J., Oldham E., Catron D., Buchanan M.E., Müller A., de Waal Malefyt R., et al. Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis. J. Immunol. 2000;164:6621-6632.

    Not in our library10.4049/jimmunol.164.12.6621

  159. 159.

    Kim T.G., Jee H., Fuentes-Duculan J., Wu W.H., Byamba D., Kim D.S., Kim D.Y., Lew D.H., Yang W.I., Krueger J.G., et al. Dermal clusters of mature dendritic cells and T cells are associated with the CCL20/CCR6 chemokine system in chronic psoriasis. J. Investig. Dermatol. 2014;134:1462-1465.

    Not in our library10.1038/jid.2013.534

  160. 160.

    Furue K., Ito T., Tsuji G., Nakahara T., Furue M. The CCL20 and CCR6 axis in psoriasis. Scand. J. Immunol. 2019.

    Not in our library10.1111/sji.12846

  161. 161.

    Bando J.K., Gilfillan S., Song C., McDonald K.G., Huang S.C., Newberry R.D., Kobayashi Y., Allan D.S.J., Carlyle J.R., Cella M., et al. The tumor necrosis factor superfamily member RANKL suppresses effector cytokine production in group 3 innate lymphoid cells. Immunity. 2018;48:1208-1219.

    Not in our library10.1016/j.immuni.2018.04.012

  162. 162.

    Talayero P., Mancebo E., Calvo-Pulido J., Rodríguez-Muñoz S., Bernardo I., Laguna-Goya R., Cano-Romero F.L., García-Sesma A., Loinaz C., Jiménez C., et al. Innate lymphoid cells groups 1 and 3 in the epithelial compartment of functional human intestinal allografts. Am. J. Transplant. 2016;16:72-82.

    Not in our library10.1111/ajt.13435

  163. 163.

    Diani M., Casciano F., Marongiu L., Longhi M., Altomare A., Pigatto P.D., Secchiero P., Gambari R., Banfi G., Manfredi A.A., et al. Increased frequency of activated CD8(+) T cell effectors in patients with psoriatic arthritis. Sci. Rep. 2019;9:10870.

    Not in our library10.1038/s41598-019-47310-5

  164. 164.

    Steel K.J.A., Srenathan U., Ridley M., Durham L.E., Wu S.Y., Ryan S.E., Hughes C.D., Chan E., Kirkham B.W., Taams L.S. Synovial IL-17A+ CD8+ T cells display a polyfunctional, pro-inflammatory and tissue-resident memory phenotype and function in psoriatic arthritis. Arthritis Rheumatol. 2019.

    Not in our library10.1002/art.41156

  165. 165.

    Campbell J.J., Ebsworth K., Ertl L.S., McMahon J.P., Newland D., Wang Y., Liu S., Miao Z., Dang T., Zhang P., et al. IL-17-secreting γδ T Cells are completely dependent upon CCR6 for homing to inflamed skin. J. Immunol. 2017;199:3129-3136.

    Not in our library10.4049/jimmunol.1700826

  166. 166.

    Ishida-Yamamoto A., Iizuka H. Differences in involucrin immunolabeling within cornified cell envelopes in normal and psoriatic epidermis. J. Investig. Dermatol. 1995;104:391-395.

    Not in our library10.1111/1523-1747.ep12665870

  167. 167.

    Caldwell C.J., Hobbs C., McKee P.H. The relationship of Ki67 and involucrin expression in proliferative, pre-neoplastic and neoplastic skin. Clin. Exp. Dermatol. 1997;22:11-16.

    Not in our library10.1046/j.1365-2230.1997.d01-232.x

  168. 168.

    Krueger J.G., Fretzin S., Suárez-Fariñas M., Haslett P.A., Phipps K.M., Cameron G.S., McColm J., Katcherian A., Cueto I., White T., et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J. Allergy Clin. Immunol. 2012;130:145-154.e9.

    Not in our library10.1016/j.jaci.2012.04.024

  169. 169.
    IL-17 Induces an Expanded Range of Downstream Genes in Reconstituted Human Epidermis Model · 2014
    No notice
  170. 170.

    Ha H.L., Wang H., Pisitkun P., Kim J.C., Tassi I., Tang W., Morasso M.I., Udey M.C., Siebenlist U. IL-17 drives psoriatic inflammation via distinct, target cell-specific mechanisms. Proc. Natl. Acad. Sci. USA. 2014;111:E3422-E3431.

    Not in our library10.1073/pnas.1400513111

  171. 171.

    Ma W.Y., Jia K., Zhang Y. IL-17 promotes keratinocyte proliferation via the downregulation of C/EBPα. Exp. Ther. Med. 2016;11:631-636.

    Not in our library10.3892/etm.2015.2939

  172. 172.

    Zenobia C., Hajishengallis G. Basic biology and role of interleukin-17 in immunity and inflammation. Periodontol. 2000. 2015;69:142-159.

    Not in our library10.1111/prd.12083

  173. 173.

    Chiricozzi A., Guttman-Yassky E., Suárez-Fariñas M., Nograles K.E., Tian S., Cardinale I., Chimenti S., Krueger J.G. Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J. Investig. Dermatol. 2011;131:677-687.

    Not in our library10.1038/jid.2010.340

  174. 174.

    Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb. Perspect. Biol. 2009;1:a001651.

    Not in our library10.1101/cshperspect.a001651

  175. 175.

    House J.S., Zhu S., Ranjan R., Linder K., Smart R.C. C/EBPalpha and C/EBPbeta are required for Sebocyte differentiation and stratified squamous differentiation in adult mouse skin. PLoS ONE. 2010;5:e9837.

    Not in our library10.1371/journal.pone.0009837

  176. 176.

    Crish J.F., Gopalakrishnan R., Bone F., Gilliam A.C., Eckert R.L. The distal and proximal regulatory regions of the involucrin gene promoter have distinct functions and are required for in vivo involucrin expression. J. Investig. Dermatol. 2006;126:305-314.

    Not in our library10.1038/sj.jid.5700019

  177. 177.

    Witte E., Kokolakis G., Witte K., Philipp S., Doecke W.D., Babel N., Wittig B.M., Warszawska K., Kurek A., Erdmann-Keding M., et al. IL-19 is a component of the pathogenetic IL-23/IL-17 cascade in psoriasis. J. Investig. Dermatol. 2014;134:2757-2767.

    Not in our library10.1038/jid.2014.308

  178. 178.

    Sun D.P., Yeh C.H., So E., Wang L.Y., Wei T.S., Chang M.S., Hsing C.H. Interleukin (IL)-19 promoted skin wound healing by increasing fibroblast keratinocyte growth factor expression. Cytokine. 2013;62:360-368.

    Not in our library10.1016/j.cyto.2013.03.017

  179. 179.

    Yang L., Fan X., Cui T., Dang E., Wang G. Nrf2 promotes keratinocyte proliferation in psoriasis through up-regulation of keratin 6, keratin 16, and keratin 17. J. Investig. Dermatol. 2017;137:2168-2176.

    Not in our library10.1016/j.jid.2017.05.015

  180. 180.

    Paladini R.D., Coulombe P.A. Directed expression of keratin 16 to the progenitor basal cells of transgenic mouse skin delays skin maturation. J. Cell Biol. 1998;142:1035-1051.

    Not in our library10.1083/jcb.142.4.1035

  181. 181.

    Acciani T.H., Suzuki T., Trapnell B.C., Le Cras T.D. Epidermal growth factor receptor signalling regulates granulocyte-macrophage colony-stimulating factor production by airway epithelial cells and established allergic airway disease. Clin. Exp. Allergy. 2016;46:317-328.

    Not in our library10.1111/cea.12612

  182. 182.

    Furue K., Ito T., Tanaka Y., Hashimoto-Hachiya A., Takemura M., Murata M., Kido-Nakahara M., Tsuji G., Nakahara T., Furue M. The EGFR-ERK/JNK-CCL20 pathway in scratched keratinocytes may underpin koebnerization in psoriasis atients. Int. J. Mol. Sci. 2020;21:434.

    Not in our library10.3390/ijms21020434

  183. 183.

    Johnston A., Gudjonsson J.E., Aphale A., Guzman A.M., Stoll S.W., Elder J.T. EGFR and IL-1 signaling synergistically promote keratinocyte antimicrobial defenses in a differentiation-dependent manner. J. Investig. Dermatol. 2011;131:329-337.

    Not in our library10.1038/jid.2010.313

  184. 184.

    Goepel L., Jacobi A., Augustin M., Radtke M.A. Rapid improvement of psoriasis in a patient with lung cancer after treatment with erlotinib. J. Eur. Acad. Dermatol. Venereol. 2018;32:e311-e313.

    Not in our library10.1111/jdv.14862

  185. 185.

    Overbeck T.R., Griesinger F. Two cases of psoriasis responding to erlotinib: Time to revisiting inhibition of epidermal growth factor receptor in psoriasis therapy? Dermatology. 2012;225:179-182.

    Not in our library10.1159/000342786

  186. 186.

    Trivin F., Boucher E., Raoul J.L. Complete sustained regression of extensive psoriasis with cetuximab combination chemotherapy. Acta Oncol. 2004;43:592-593.

    Not in our library10.1080/02841860410020211

  187. 187.

    Neyns B., Meert V., Vandenbroucke F. Cetuximab treatment in a patient with metastatic colorectal cancer and psoriasis. Curr. Oncol. 2008;15:196-197.

    Not in our library10.3747/co.v15i4.228

  188. 188.

    Carrier Y., Ma H.L., Ramon H.E., Napierata L., Small C., O’Toole M., Young D.A., Fouser L.A., Nickerson-Nutter C., Collins M., et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: Implications in psoriasis pathogenesis. J. Investig. Dermatol. 2011;131:2428-2437.

    Not in our library10.1038/jid.2011.234

  189. 189.

    Gläser R., Meyer-Hoffert U., Harder J., Cordes J., Wittersheim M., Kobliakova J., Fölster-Holst R., Proksch E., Schröder J.M., Schwarz T. The antimicrobial protein psoriasin (S100A7) is upregulated in atopic dermatitis and after experimental skin barrier disruption. J. Investig. Dermatol. 2009;129:641-649.

    Not in our library10.1038/jid.2008.268

  190. 190.

    Nograles K.E., Zaba L.C., Guttman-Yassky E., Fuentes-Duculan J., Suárez-Fariñas M., Cardinale I., Khatcherian A., Gonzalez J., Pierson K.C., White T.R., et al. Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br. J. Dermatol. 2008;159:1092-1102.

    Not in our library10.1111/j.1365-2133.2008.08769.x

  191. 191.

    Baggiolini M. Chemokines in pathology and medicine. J. Intern. Med. 2001;250:91-104.

    Not in our library10.1046/j.1365-2796.2001.00867.x

  192. 192.

    Johnston A., Xing X., Wolterink L., Barnes D.H., Yin Z., Reingold L., Kahlenberg J.M., Harms P.W., Gudjonsson J.E. IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis. J. Allergy Clin. Immunol. 2017;140:109-120.

    Not in our library10.1016/j.jaci.2016.08.056

  193. 193.

    Nedoszytko B., Sokołowska-Wojdyło M., Ruckemann-Dziurdzińska K., Roszkiewicz J., Nowicki R.J. Chemokines and cytokines network in the pathogenesis of the inflammatory skin diseases: Atopic dermatitis, psoriasis and skin mastocytosis. Postepy. Dermatol. Alergol. 2014;31:84-91.

    Not in our library10.5114/pdia.2014.40920

  194. 194.

    Li N., Yamasaki K., Saito R., Fukushi-Takahashi S., Shimada-Omori R., Asano M., Aiba S. Alarmin function of cathelicidin antimicrobial peptide LL37 through IL-36γ induction in human epidermal keratinocytes. J. Immunol. 2014;193:5140-5148.

    Not in our library10.4049/jimmunol.1302574

  195. 195.

    Henry C.M., Sullivan G.P., Clancy D.M., Afonina I.S., Kulms D., Martin S.J. Neutrophil-derived proteases escalate inflammation through activation of IL-36 family cytokines. Cell Rep. 2016;14:708-722.

    Not in our library10.1016/j.celrep.2015.12.072

  196. 196.

    Pfaff C.M., Marquardt Y., Fietkau K., Baron J.M., Lüscher B. The psoriasis-associated IL-17A induces and cooperates with IL-36 cytokines to control keratinocyte differentiation and function. Sci. Rep. 2017;7:15631.

    Not in our library10.1038/s41598-017-15892-7

  197. 197.

    Muhr P., Zeitvogel J., Heitland I., Werfel T., Wittmann M. Expression of interleukin (IL)-1 family members upon stimulation with IL-17 differs in keratinocytes derived from patients with psoriasis and healthy donors. Br. J. Dermatol. 2011;165:189-193.

    Not in our library10.1111/j.1365-2133.2011.10302.x

  198. 198.

    Gabay C., Towne J.E. Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions. J. Leukoc. Biol. 2015;97:645-652.

    Not in our library10.1189/jlb.3ri1014-495r

  199. 199.
    The Significance of IL-36 Hyperactivation and IL-36R Targeting in Psoriasis · 2019
    No notice
  200. 200.

    Bachelez H., Choon S.E., Marrakchi S., Burden A.D., Tsai T.F., Morita A., Turki H., Hall D.B., Shear M., Baum P., et al. Inhibition of the interleukin-36 pathway for the treatment of generalized pustular psoriasis. N. Engl. J. Med. 2019;380:981-983.

    Not in our library10.1056/nejmc1811317

  201. 201.

    Furue K., Ito T., Tanaka Y., Yumine A., Hashimoto-Hachiya A., Takemura M., Murata M., Yamamura K., Tsuji G., Furue M. Cyto/chemokine profile of in vitro scratched keratinocyte model: Implications of significant upregulation of CCL20, CXCL8 and IL36G in Koebner phenomenon. J. Dermatol. Sci. 2019;94:244-251.

    Not in our library10.1016/j.jdermsci.2019.04.002

  202. 202.

    Maecker H.T., McCoy J.P., Nussenblatt R. Standardizing immunophenotyping for the Human Immunology Project. Nat. Rev. Immunol. 2012;12:191-200.

    Not in our library10.1038/nri3158

  203. 203.

    Singh S.P., Zhang H.H., Foley J.F., Hedrick M.N., Farber J.M. Human T cells that are able to produce IL-17 express the chemokine receptor CCR6. J. Immunol. 2008;180:214-221.

    Not in our library10.4049/jimmunol.180.1.214

  204. 204.

    Harper E.G., Guo C., Rizzo H., Lillis J.V., Kurtz S.E., Skorcheva I., Purdy D., Fitch E., Iordanov M., Blauvelt A. Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: Implications for psoriasis pathogenesis. J. Investig. Dermatol. 2009;129:2175-2183.

    Not in our library10.1038/jid.2009.65

  205. 205.

    Bouma G., Zamuner S., Hicks K., Want A., Oliveira J., Choudhury A., Brett S., Robertson D., Felton L., Norris V., et al. CCL20 neutralization by a monoclonal antibody in healthy subjects selectively inhibits recruitment of CCR6(+) cells in an experimental suction blister. Br. J. Clin. Pharmacol. 2017;83:1976-1990.

    Not in our library10.1111/bcp.13286

  206. 206.

    Robert R., Ang C., Sun G., Juglair L., Lim E.X., Mason L.J., Payne N.L., Bernard C.C., Mackay C.R. Essential role for CCR6 in certain inflammatory diseases demonstrated using specific antagonist and knockin mice. JCI. Insight. 2017;2.

    Not in our library10.1172/jci.insight.94821

  207. 207.

    Tawaraishi T., Sakauchi N., Hidaka K., Yoshikawa K., Okui T., Kuno H., Chisaki I., Aso K. Identification of a novel series of potent and selective CCR6 inhibitors as biological probes. Bioorg. Med. Chem. Lett. 2018;28:3067-3072.

    Not in our library10.1016/j.bmcl.2018.07.042

  208. 208.

    Campbell J.J., Ebsworth K., Ertl L.S., McMahon J.P., Wang Y., Yau S., Mali V.R., Chhina V., Kumamoto A., Liu S., et al. Efficacy of chemokine receptor inhibition in treating IL-36α-induced psoriasiform inflammation. J. Immunol. 2019;202:1687-1692.

    Not in our library10.4049/jimmunol.1801519

  209. 209.

    Mose M., Kang Z., Raaby L., Iversen L., Johansen C. TNFα- and IL-17A-mediated S100A8 expression is regulated by p38 MAPK. Exp. Dermatol. 2013;22:476-481.

    Not in our library10.1111/exd.12187

  210. 210.

    Liang S.C., Tan X.Y., Luxenberg D.P., Karim R., Dunussi-Joannopoulos K., Collins M., Fouser L.A. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. Exp. Med. 2006;203:2271-2279.

    Not in our library10.1084/jem.20061308

  211. 211.

    D’Amico F., Skarmoutsou E., Granata M., Trovato C., Rossi G.A., Mazzarino M.C. S100A7: A rAMPing up AMP molecule in psoriasis. Cytokine Growth Factor Rev. 2016;32:97-104.

    Not in our library10.1016/j.cytogfr.2016.01.002

  212. 212.

    Sa S.M., Valdez P.A., Wu J., Jung K., Zhong F., Hall L., Kasman I., Winer J., Modrusan Z., Danilenko D.M., et al. The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. J. Immunol. 2007;178:2229-2240.

    Not in our library10.4049/jimmunol.178.4.2229

  213. 213.

    Hegyi Z., Zwicker S., Bureik D., Peric M., Koglin S., Batycka-Baran A., Prinz J.C., Ruzicka T., Schauber J., Wolf R. Vitamin D analog calcipotriol suppresses the Th17 cytokine-induced proinflammatory S100 “alarmins” psoriasin (S100A7) and koebnerisin (S100A15) in psoriasis. J. Investig. Dermatol. 2012;132:1416-1424.

    Not in our library10.1038/jid.2011.486

  214. 214.

    Hsu K., Champaiboon C., Guenther B.D., Sorenson B.S., Khammanivong A., Ross K.F., Geczy C.L., Herzberg M.C. Anti-infective protective properties of S100 calgranulins. Antiinflamm. Antiallergy Agents Med. Chem. 2009;8:290-305.

    Not in our library10.2174/187152309789838975

  215. 215.

    Kolbinger F., Loesche C., Valentin M.A., Jiang X., Cheng Y., Jarvis P., Peters T., Calonder C., Bruin G., Polus F., et al. β-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis. J. Allergy Clin. Immunol. 2017;139:923-932.

    Not in our library10.1016/j.jaci.2016.06.038

  216. 216.

    Yan W.X., Armishaw C., Goyette J., Yang Z., Cai H., Alewood P., Geczy C.L. Mast cell and monocyte recruitment by S100A12 and its hinge domain. J. Biol. Chem. 2008;283:13035-13043.

    Not in our library10.1074/jbc.m710388200

  217. 217.

    Nukui T., Ehama R., Sakaguchi M., Sonegawa H., Katagiri C., Hibino T., Huh N.H. S100A8/A9, a key mediator for positive feedback growth stimulation of normal human keratinocytes. J. Cell Biochem. 2008;104:453-464.

    Not in our library10.1002/jcb.21639

  218. 218.

    Muta T. IkappaB-zeta: An inducible regulator of nuclear factor-kappaB. Vitam. Horm. 2006;74:301-316.

    Not in our library10.1016/s0083-6729(06)74012-2

  219. 219.

    Bertelsen T., Iversen L., Johansen C. The human IL-17A/F heterodimer regulates psoriasis-associated genes through IκBζ. Exp. Dermatol. 2018;27:1048-1052.

    Not in our library10.1111/exd.13722

  220. 220.

    Muromoto R., Hirao T., Tawa K., Hirashima K., Kon S., Kitai Y., Matsuda T. IL-17A plays a central role in the expression of psoriasis signature genes through the induction of IκB-ζ in keratinocytes. Int. Immunol. 2016;28:443-452.

    Not in our library10.1093/intimm/dxw011

  221. 221.

    Dorschner R.A., Pestonjamasp V.K., Tamakuwala S., Ohtake T., Rudisill J., Nizet V., Agerberth B., Gudmundsson G.H., Gallo R.L. Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. J. Investig. Dermatol. 2001;117:91-97.

    Not in our library10.1046/j.1523-1747.2001.01340.x

  222. 222.

    Reinholz M., Ruzicka T., Schauber J. Cathelicidin LL-37: An antimicrobial peptide with a role in inflammatory skin disease. Ann. Dermatol. 2012;24:126-135.

    Not in our library10.5021/ad.2012.24.2.126

  223. 223.

    Tomasinsig L., Pizzirani C., Skerlavaj B., Pellegatti P., Gulinelli S., Tossi A., Di Virgilio F., Zanetti M. The human cathelicidin LL-37 modulates the activities of the P2X7 receptor in a structure-dependent manner. J. Biol. Chem. 2008;283:30471-30481.

    Not in our library10.1074/jbc.m802185200

  224. 224.

    Di Nardo A., Braff M.H., Taylor K.R., Na C., Granstein R.D., McInturff J.E., Krutzik S., Modlin R.L., Gallo R.L. Cathelicidin antimicrobial peptides block dendritic cell TLR4 activation and allergic contact sensitization. J. Immunol. 2007;178:1829-1834.

    Not in our library10.4049/jimmunol.178.3.1829

  225. 225.

    Tokumaru S., Sayama K., Shirakata Y., Komatsuzawa H., Ouhara K., Hanakawa Y., Yahata Y., Dai X., Tohyama M., Nagai H., et al. Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. J. Immunol. 2005;175:4662-4668.

    Not in our library10.4049/jimmunol.175.7.4662

  226. 226.
    Neutrophil extracellular trap formation is increased in psoriasis and induces human β-defensin-2 production in epidermal keratinocytes · 2016
    No notice
  227. 227.

    Lande R., Gregorio J., Facchinetti V., Chatterjee B., Wang Y.H., Homey B., Cao W., Wang Y.H., Su B., Nestle F.O., et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449:564-569.

    Not in our library10.1038/nature06116

  228. 228.

    Mabuchi T., Hirayama N. Binding affinity and interaction of LL-37 with HLA-C*06:02 in psoriasis. J. Investig. Dermatol. 2016;136:1901-1903.

    Not in our library10.1016/j.jid.2016.04.033

  229. 229.

    Takahashi T., Kulkarni N.N., Lee E.Y., Zhang L.J., Wong G.C.L., Gallo R.L. Cathelicidin promotes inflammation by enabling binding of self-RNA to cell surface scavenger receptors. Sci. Rep. 2018;8:4032.

    Not in our library10.1038/s41598-018-22409-3

  230. 230.

    Ong P.Y., Ohtake T., Brandt C., Strickland I., Boguniewicz M., Ganz T., Gallo R.L., Leung D.Y. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N. Engl. J. Med. 2002;347:1151-1160.

    Not in our library10.1056/nejmoa021481

  231. 231.

    de Jongh G.J., Zeeuwen P.L., Kucharekova M., Pfundt R., van der Valk P.G., Blokx W., Dogan A., Hiemstra P.S., van de Kerkhof P.C., Schalkwijk J. High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis. J. Investig. Dermatol. 2005;125:1163-1173.

    Not in our library10.1111/j.0022-202x.2005.23935.x

  232. 232.

    Nomura I., Goleva E., Howell M.D., Hamid Q.A., Ong P.Y., Hall C.F., Darst M.A., Gao B., Boguniewicz M., Travers J.B., et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J. Immunol. 2003;171:3262-3269.

    Not in our library10.4049/jimmunol.171.6.3262

  233. 233.

    Yang D., Chertov O., Bykovskaia S.N., Chen Q., Buffo M.J., Shogan J., Anderson M., Schröder J.M., Wang J.M., Howard O.M., et al. Beta-defensins: Linking innate and adaptive immunity through dendritic and T cell CCR6. Science. 1999;286:525-528.

    Not in our library10.1126/science.286.5439.525

  234. 234.

    Ghannam S., Dejou C., Pedretti N., Giot J.P., Dorgham K., Boukhaddaoui H., Deleuze V., Bernard F.X., Jorgensen C., Yssel H., et al. CCL20 and β-defensin-2 induce arrest of human Th17 cells on inflamed endothelium in vitro under flow conditions. J. Immunol. 2011;186:1411-1420.

    Not in our library10.4049/jimmunol.1000597

Cited by papers we hold 8

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.