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The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

Taoming Liu, Sheng Li, Shuni Ying and 5 more

Frontiers in Immunology · 2020 · Review · CC BY

doi:10.3389/fimmu.2020.594735

Abstract

helper T cells (Th17 cells) and subsets of innate lymphoid cells. IL-17A is associated with the pathogenesis of inflammatory diseases, including psoriasis, atopic dermatitis, hidradenitis suppurativa, alopecia areata, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Interleukin-23 (IL-23) plays a pivotal role in stimulating the production of IL-17 by activating the Th17 cells. The IL-23/IL-17 axis is an important pathway for targeted therapy for inflammatory diseases. Emerging evidence from clinical trials has shown that monoclonal antibodies against IL-23, IL-17, and tumor necrosis factor are effective in the treatment of patients with psoriasis, atopic dermatitis, hidradenitis suppurativa, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Here, we summarize the latest knowledge about the biology, signaling, and pathophysiological functions of the IL-23/IL-17 axis in inflammatory skin diseases. The currently available biologics targeting the axis is also discussed.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 18, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

Interleukin-17A (IL-17A) is cloned from a T cell hybridoma activated in rodents and is related to several immune-mediated disorders, such as autoimmune, oncogenic, and infectious diseases. The T helper 17 (Th17) cells constitute a unique subset of CD4+ T cells and are the major source of IL-17. IL-17A triggers cellular reactions not only in the keratinocytes, but also in some other cells, including neutrophils, endothelial cells, fibroblasts, and osteoclasts. In keratinocytes, the binding of IL-17A to IL-17 receptor (IL-17R) A, IL-17C, or IL-17RD stimulates keratinocyte proliferation. Subsequently, the release of inflammatory mediators and chemokines leads to inflammatory reaction.

The cytokines, interleukin-23 (IL-23) and IL-17, have been confirmed to markedly affect chronic inflammation. In addition, the discovery of the IL-23/IL-17 pathway has contributed to a clearer understanding of the underlying mechanism of inflammatory diseases. At present, therapies for inflammatory diseases have advanced from general immunosuppression to biologics against the IL-23/IL-17 signaling pathway, such as IL-17, IL-12/23 and IL-23 inhibitors. In this review, we highlight the potential implications of dysregulation of the IL-23/IL-17 axis in chronic inflammatory skin diseases, including psoriasis, hidradenitis suppurativa (HS), atopic dermatitis (AD), alopecia areata (AA), pityriasis rubra pilaris (PRP), pemphigus, and systemic sclerosis (SSc).

Search Strategy and Selection Criteria

In this review, we are not intended to comprehensively review all pathways identified through human and murine laboratory studies or all clinical trials and case series in various inflammatory skin diseases. Nevertheless, we intent to focus on those targets of IL-23/IL-17 pathway demonstrated to be effective or potentially effective for treating human inflammatory skin diseases. We searched the published literature from PubMed and ClinicalTrial.gov with the search terms including ‘IL-17,’ ‘psoriasis,’ ‘atopic dermatitis,’ ‘hidradenitis suppurativa,’ ‘alopecia areata,’ ‘pityriasis rubra pilaris,’ ‘pemphigus,’ ‘systemic sclerosis,’ ‘secukinumab,’ ‘ixekizumab,’ ‘brodalumab,’ ‘bimekizumab,’ ‘ustekinumab,’ ‘tildrakizumab,’ ‘guselkumab,’ and ‘risankizumab’. We mainly focused on publications written in English between September 1, 2010, and September 15, 2020. We chose the references depending on the basis of their originality and relevance to the topic.

IL-17 Signaling in Inflammatory and Autoimmune Diseases

Th17 cells are known to play an important role in inflammatory and autoimmune diseases. In general, IL-23 is involved in the activation of Th17 cells to induce the production of IL-17A, IL-17F, tumor necrosis factor (TNF), and IL-6. Binding to its receptors, IL-23 contributes to the phosphorylation of receptor-associated JAKs and specific Tyr residues, and this is followed by activating the transcription of IL-17 and other genes. The participation of IL-23 is crucial in the differentiation of IL-17-expressing phenotypes, via activating the transcription factor retinoid-related orphan receptor-γt (ROR-γt) and signal transducer and activator of transcription 3 (STAT3).

IL-17 induces expression of downstream genes by stimulating activation of pathways, including canonical nuclear factor-κB (NF-κB), CCAAT/enhancer-binding protein (C/EBP) family, and mitogen-activated protein kinase (MAPK) (Figure 1). The key complex, which is consisted of IL-17A/A, IL-17A/F, or IL-17F/F cytokine and IL-17RA or IL-17RC, is the start hallmark of IL-17 signaling transduction. Moreover, IL-17RD is also found to be a functional receptor for IL-17A groups. Together with IL-17RC, IL-17RD acts on the downstream of proinflammatory gene expression of IL-17 signaling. IL-17R is characterized by a unique structure in its cytoplasmic tail, termed SEF/IL-17R (SEFIR) domain. IL-17 signaling recruits Act1 to IL-17R through interaction platform of SEFIR domain. Then Act1 (also known as an E3 ligase) promotes activation of distinct downstream signaling cascades by tumor-necrosis factor receptor–associated factor (TRAF) 6. TRAF6 then recruits and stimulates the transforming growth factor β-activated kinase 1 and the inhibitor of kappa B kinase complex, resulting in activation of NF-κB, C/EBPβ, C/EBPδ, and MAPK pathway. IL-17R-Act1 complex binds with MEKK3 and MEK5, leading to keratinocyte proliferation. Act1 binds with TRAF2-TRAF5 to maintain the mRNA stability targeting IL-17 gene. In contrast, TRAF3 triggers a negative reaction in activation of NF-κB and MAPK pathway, resulting in suppressing the formation of IL-17R-Act1-TRAF6. TRAF6, in combination with A20 (an anti-inflammatory protein) when presented, blocks the activation of NF-κB and MAPK to negatively regulate IL-17 signaling.

Role of IL-17 Family Members in Psoriasis

In patients with psoriasis, the IL-17 concentrations increase not only in the skin lesions and peripheral blood, but also in the nonlesional and uninvolved skin. There is evidence indicating that the main sources of IL-17A in patients with psoriasis are the neutrophils, Th17 cells, mast cells, CD8+ T cells, αβ T, γδ T cells, and innate lymphoid cells in the skin lesions.

Psoriasis autoantigens, such as LL37, NFKBIZ, ADAMTSL5, and CARMA2, play a crucial role in the production of IL-17A and are involved in the pathogenesis of psoriasis. In psoriasis, the combination of LL37 with the patient’s own DNA leads to the activation of the Toll-like receptor 9. The self-DNA-LL37 complex acts on Toll-like receptor 7 in the plasmacytoid dendritic cells (DCs) and triggers the activation of the classical myeloid DCs (Figure 2). Subsequently, the myeloid DCs produce IL-12 and IL-23. IL-23 induces the differentiation of the CD4+ T cells into the Th1 cells and Th17 cells by stimulating the transcription factor ROR-γt and STAT3. Thereafter, the activated Th17 cells secrete Th17 cytokines (IL-17A, IL-22, and TNF-α), leading to the development of a positive feedback loop. IL-17 plays a key role in stimulating the NF-κB and MAPK signaling pathways, contributing to a high expression of proinflammatory factors (CC-chemokine ligand 20 and CC-chemokine receptor 6). These proinflammatory cytokines and chemokines recruit the inflammatory cells and stimulate keratinocyte proliferation.

IL-17A plays an essential role in inflammation, metabolism, and bone/joint damage. The IL-17 levels and Th17 cell frequencies are high in the skin, synovial fluid, and synovium tissue of the patients with psoriatic arthritis (PsA). In the synovium of patients with PsA, the mast cells and CD8+ T cells are the main sources of IL-17A. The aberrant expression of IL-17A directly affects the osteoclast precursors, leading to bone destruction in PsA. In addition, IL-17A interacts with the mediators of the Wnt signaling pathway in the osteoblasts and osteocytes, thus, preventing bone formation. Psoriatic inflammation is not restricted to the skin or joints. Metabolic disorders, such as hyperglycemia and cardiovascular risks, are also associated with psoriasis.

Apart from IL-17A, the other IL-17 family members (IL-17C, E, and F) may also be involved in the pathogenesis of psoriasis. In contrast to that in the nonlesional psoriatic skin, mRNA expression of IL-17A, IL-17C, IL-17E, and IL-17F is increased in the lesional psoriatic skin. The IL-17C and IL-17E levels are higher than the IL-17A levels in the skin lesions in the psoriatic animal models. Through the STAT3 pathway, the binding of IL-17E to IL-17RB induces keratinocyte proliferation to amplify skin inflammation in the psoriatic animal models. However, the effects of IL17-C on the mechanisms of psoriasis are not clear. Both IL-17F and IL-17A share homomeric and heterodimeric proteins with 50% sequence identity. The molecular structure and function of IL-17F are highly similar to those of IL-17A. Bimekizumab (an inhibitor of both IL-17A and IL-17F) is more effective than a blockade of IL-17A or IL-17F alone, especially for suppressing neutrophil chemotaxis and activating the synoviocytes or human dermal fibroblasts in vitro.

Targeted Therapy in Psoriasis

The targeted biologics in the treatment of psoriasis are listed in Supplementary Table. Biologics targeting IL-23 or IL-17A have shown remarkable effects in the treatment of psoriasis. The anti-IL-17 agents approved by the FDA include secukinumab (anti-IL-17A), ixekizumab (anti-IL-17A), brodalumab (anti-IL-17RA), and bimekizumab (anti-IL-17A and -17F). Biologics against IL-23 include ustekinumab (anti-IL-12/23p40), tildrakizumab (anti-IL-23p19), guselkumab (anti-IL-23p19), and risankizumab (anti-IL-23p19).

Secukinumab

Secukinumab, a human immunoglobulin G1 monoclonal antibody against IL-17A, is an effective and safe biologic for psoriasis, involving skin, nails, and PsA. The data from the phase III randomized trials (ERASURE and FIXTURE) showed that secukinumab at doses of 300 or 150 mg is effective and safe for the treatment of moderate-to-severe psoriasis up to week 52 (Supplementary Table). Secukinumab maintains significant powerful and long-lasting effects on the patients receiving the 300 mg secukinumab treatment every 4 weeks. The Psoriasis Area and Severity Index (PASI) 90/100 was 66.4%/41% at 156 weeks.

In the FUTURE 2 study, patients with PsA receiving secukinumab therapy achieved excellent and sustained improvement in the PASI90 and American College of Rheumatology 50 (ACR50) response at week 24 (Supplementary Table). The results for patients who continued the study showed that, at week 104, the ACR50 response rates were 50.6 and 36% with the 300 and 150 mg doses of secukinumab, respectively. Secukinumab is important in suppressing synovitis and structural bone changes in patients with PsA at week 24, and low rates of radiographic progression are maintained at week 52 with secukinumab.

Secukinumab has significant and long-term efficacy for the treatment of nail psoriasis. Therefore, the improvement in the Nail Psoriasis Severity Index (NAPSI) in the secukinumab 300 and secukinumab 150 groups was 73 and 63.6% at week 128, respectively. In summary, secukinumab shows excellent and sustained efficacy for the treatment of patients with moderate-to-severe plaque psoriasis and patients with psoriasis with or without arthritis and nail involvement.

Ixekizumab

Ixekizumab, a humanized immunoglobulin G4 monoclonal antibody, selectively blocks IL-17A. A multicenter trial (UNCOVER-3) reported that ixekizumab shows long-term efficacy for treating moderate-to-severe plaque psoriasis and that the treatment effects are strongly sustained for up to 156 weeks (Supplementary Table). Similarly, ixekizumab maintains promising clinical improvements in the scalp, nails, and palm.

According to the data from phase III studies (SPIRIT-P1 and SPIRIT-P2), ixekizumab is associated with improvements in disease prognosis and physical function in patients with active PsA, particularly, in those who are refractory to therapies or have an inadequate response to the anti-TNF therapies (Supplementary Table). To date, blockade of IL-17A is being advocated as first-line for treatment of PsA by the European League Against Rheumatism in 2019. In general, the aforementioned studies suggest that ixekizumab is effective in controlling psoriasis and PsA, particularly in patients with lesions in hard-to-treat areas or in those who are refractory to treatments.

Brodalumab

Brodalumab, a fully human immunoglobulin G2 IL-17RA antagonist, leads to a rapid improvement in the molecular, histological, and clinical features of psoriasis at week 12. The AMAAGINE-1 study showed that brodalumab shows sustained efficacy (120 weeks) in the treatment of moderate-to-severe plaque psoriasis (Supplementary Table). Brodalumab inhibits a broader range of targets, namely, IL-17AA, IL-17AF, IL-17FF, IL-17C, and IL-17E via IL-17RA, compared with secukinumab and ixekizumab. An open-label study involving 39 patients with moderate-to-severe psoriasis revealed that brodalumab treatment may be effective for the patients who did not respond to secukinumab, ixekizumab, or ustekinumab.

Moreover, the data from an open-label study have indicated significant beneficial effect of brodalumab on psoriatic erythroderma (n = 18) and generalized pustular psoriasis (n = 12; Supplementary Table). However, the sample size of this study was small; hence, multicenter trials with large sample sizes of patients with psoriatic erythroderma or generalized pustular psoriasis should be conducted.

Bimekizumab

Bimekizumab, a humanized monoclonal IgG1 antagonist neutralizing both IL-17A and IL-17F, is effective for PsA and moderate-to-severe plaque psoriasis. Two phase II trials (BE ABLE 1 and BE ABLE 2) reported the safety and efficacy of bimekizumab for the treatment of moderate-to-severe plaque psoriasis (Supplementary Table). Patients with active PsA, who were administered bimekizumab, showed marked improvements in their condition at week 48 (Supplementary Table).

Adverse Events of Targeting IL-17 Therapy

The most commonly noted treatment-emergent adverse events (TEAEs) are infections, nasopharyngitis, headache, and diarrhea in patients treated with IL-17 inhibitors compared with those treated with a placebo. A systematic review speculated that it was safe to use IL-17 antagonists (secukinumab, ixekizumab, and brodalumab) for patients with psoriasis with latent tuberculosis infection. However, eczematous eruptions were reported in some patients after treatment with biologics against IL-17A (secukinumab or ixekizumab) for 3–4 months. To date, the mechanism underlying the onset of eczematous adverse events after anti-IL-17A treatment is not clear. Both the Th1 and Th2 responses are involved in the pathogenesis of eczema. This may be due to the anti-IL-17 biologics mainly inhibit the Th17 cytokines and mediate an imbalance in the Th2/Th17 immune response, thus leading to eczematous eruptions. The deficiency of Th17 cells, IL-17RA, and IL-17F are essential for host defense against fungal pathogens in mucocutaneous and oral epithelial cells. The risk of chronic mucocutaneous candidiasis increases in patients received IL-17 blockades (secukinumab, ixekizumab, brodalumab, or bimekizumab).

Targeting IL-23

Ustekinumab, a humanized IgG1 monoclonal antibody against the p40 subunit of IL-12 and IL-23, is approved for treating adult and pediatric patients with moderate-to-severe plaque psoriasis. Two phase III trials (PHOENIX 1 and PHOENIX 2) reported rapid and sustained efficacy of ustekinumab when administered at doses of 45 mg or 90 mg every 12 weeks for patients with moderate-to-severe plaque psoriasis (Supplementary Table).

According to the phase IV trial (VIP-U), ustekinumab may reduce aortic vascular inflammation transiently (at week 12) and downregulate the expression of the inflammatory cytokines (TNF-α, IL-1β, IL-17A, IL-18, and IL-6) sustainably (at week 52). In 25 patients with psoriasis, inflammation in the liver, spleen, and artery decreased after treatment with ustekinumab, as indicated by the radiography findings. A summary analysis indicated that ustekinumab has long-term (5 years) safety with respect to patients with moderate-to-severe psoriasis.

Risankizumab, a humanized IgG1 monoclonal antibody inhibits the p19 subunit of IL-23. In the landmark UltIMMa-1 and UltIMMa-2 studies, 150 mg risankizumab proved beneficial in the treatment of moderate-to-severe psoriasis compared with a placebo and ustekinumab (Supplementary Table).

Tildrakizumab is a humanized IgG1 monoclonal antagonist, targeting IL-23p19. The data from reSURFACE 1 and reSURFACE 2 have indicated significant safety and efficacy of tildrakizumab for the treatment of chronic plaque psoriasis; moreover, tildrakizumab was well-tolerated by the patients (Supplementary Table). A pooled analysis of three trials showed that tildrakizumab maintains beneficial impact and low rates of serious TEAEs. The PASI75 scores of patients continuously treated with 100 mg and 200 mg tildrakizumab at 64 weeks were 86 and 83%, respectively.

Guselkumab, a human monoclonal anti-IL-23p19 antagonist, is used for the treatment of PsA. Two phase III trials (DISCOVER-1 and DISCOVER-2) showed that patients with PsA treated with guselkumab showed excellent and rapid, improvements in their condition; moreover, guselkumab treatment was safe for these patients. The results of the trials revealed that, at week 24, the ACR20 response rates were 52 and 64% for guselkumab administered every 4 weeks and 8 weeks, respectively (Supplementary Table).

In summary, the aforementioned clinical trials reported that anti-IL-23 antibodies can successfully control psoriasis and PsA. However, the long-term follow-up data on anti-IL-23p19 biologics are limited. Multicenter studies with large sample sizes should be conducted in the future to evaluate the long-term efficacy and safety of these antagonists.

Role of IL-17 in Hidradenitis Suppurativa

HS is a Th1/Th17-driven inflammatory skin disease (Figure 2). The histopathological analysis of skin biopsy samples has revealed that the frequencies of the Th17 cells and regulatory T (Treg) cells are elevated in the lesional HS skin. The levels of inflammatory cytokines (IL-17, IL-23, IL-1β, TNF-α, and IL-12) are high in the lesional, perilesional, and uninvolved skin of patients with HS. The serum levels of IL-17 and S100A8/A9 are higher in the patients with HS than in healthy individuals.

The neutrophils and Th17 cells are the major sources of IL-17 in HS; in contrast, the keratinocytes are a key source of proinflammatory molecules, including S100A8/A9, NACHT, LRR, and PYD domains-containing protein 3, and caspase-1. Notably, HS showed histopathological changes characteristic of epidermal psoriasiform hyperplasia, follicular plugging, and infiltration of low-grade leucocytes in the uninvolved skin of perilesional HS. In such microenvironments, the IL-17-stimulated keratocytes show upregulation of the expression of the proinflammatory proteins (S100A8/A9) and promotion of the release of IL-1β by activation of the NACHT, LRR, and PYD domains-containing protein 3. Consequently, large amounts of proinflammatory molecules are recruited to promote the influx of the neutrophils, which, in turn, upregulate the release of IL-17 and S100A8/A9; thus, a positive-feedback loop of the inflammatory response is maintained (Figure 2).

Targeted Therapy in Hidradenitis Suppurativa

An open-label and single-site exploratory trial has reported the efficacy of targeting IL-17A with secukinumab in the treatment of HS. The nine patients administrated of 300 mg secukinumab once a week from baseline for 5 weeks and then every 4 weeks. At 24 weeks, 67% patients with HS achieved Hidradenitis Suppurativa Clinical Response (HiSCR) score. Very recently, an open-label pilot cohort study on 10 patients assessed the well tolerability and clinical response of brodalumab in the treatment of moderate to severe HS. It demonstrated that patients received 210 mg brodalumab achieving HiSCR at week 12, and HiSCR improvement occurred as early as week 2. An open-label study indicates that, at week 40, a moderate-to-marked improvement of the modified Sartorius score was achieved in 82% (14/17) of patients with HS receiving IL-12/23 biologic ustekinumab therapy. The data on the efficacy and safety of biologics for treating HS are limited, and further studies with adequate sample sizes are required to establish the effective and long-term impact of treatment.

Atopic Dermatitis

Traditionally, AD was considered a Th2 immune response with elevated levels of IgE. Studies have revealed that the Th1, Th2, Th22, and Th17 cells are involved in the pathogenesis of AD (Figure 2). It has been demonstrated that Th22 and Th17 immune responses contribute to chronic skin lesions of AD, especially in pediatric, intrinsic, and Asian patients.

IL-17E (also called IL-25) level increases in the epidermis in patients with AD. In keratinocytes, the null mutation of filaggrin gene (FLG) is associated with the skin barrier dysfunction, increasing the risk of AD. FLG synthesis is suppressed by IL-17E in the keratinocytes. Moreover, the data from mouse models indicated that IL-17E induces the type 2 innate lymphoid cells to produce type 2 cytokines (IL-5 and IL-13).

To investigate the efficacy of anti-IL-17A biologics in AD, a randomized phase II trial was conducted involving 41 patients who were administered secukinumab. However, the trial results showed that at week 16, both clinical assessments (the Scoring Atopic Dermatitis index and Eczema Area and Severity Index) and lesional skin immunohistochemical analysis of patients receiving secukinumab revealed no significant improvement compared with those receiving a placebo. This trial demonstrated that IL17 is not a pivotal contributor to the pathogenesis of AD, even in the subsets of patients with higher Th17 activation.

Although ustekinumab showed promising efficacy in a review which included published case reports and case series, no efficacy was observed in randomized controlled trials of targeting IL-12/23 for treating patients with AD. Additional studies with large sample sizes and may show the efficacy of ustekinumab in treating AD.

Alopecia Areata

AA is a common inflammatory skin disorder, which is characterized by nonscarring hair loss via infiltration of the CD8+ T cells and increase in the levels of cytokines (IFN-γ, TNF-α, IL-17 and IL-4; Figure 2). IL-2, IFN-γ, IL-10, IL-13, and IL-17A are expressed at high levels in the serum of patients with AA, while the level of transforming growth factor -β1 is decreased. The Th17 cell frequencies and IL-17 levels significantly increased both in the peripheral blood and scalp lesions in patients with AA; however, the frequency of Treg cells decreased. Studies have reported that patients with AA do not show any response to the administration of anti-IL-23/IL-12 ustekinumab (n = 4) or anti-IL-17A secukinumab (n = 7). Therefore, it cannot be concluded the contribution of Th17/IL-17 in the pathogenesis of AA. Further clinical trials with large sample size may reveal the value of IL-17 as a target of AA.

Pityriasis Rubra Pilaris

PRP is a rare acquired inflammatory skin disease. The levels of Th17 and Th1 cytokines increase in the lesional skin of the patients with PRP, including IL-17A, IL-17F, IL-22, TNF, IL-6, IL-12, IL-23, and IL-1β. The IL-23/Th17 axis seems to be important in the pathogenesis of PRP due to the clinical and histopathologic improvement in the targeting IL-12/23 and IL-17A (ustekinumab, secukinumab, and ixekizumab) treatment of patients with PRP. In a single-armed trial, analyzing changes in the clinical signs and symptoms (using PASI scores) showed that PASI50, PASI75 and PASI90 response rates were 58, 42, and 17% respectively during ixekizumab treatment of PRP at week 24. For those 5 patients who failed to conventional therapies, all of them have achieved clinical improvement from ustekinumab, particularly, changes in decreased erythema, follicular hyperkeratosis, and scaling during a 15-month follow-up period.

Pemphigus

In the serum and lesional skin of patients with pemphigus vulgaris, the levels of IL-23 and IL-17 increase, both are significantly correlated with diseases severity. The frequency of CD4+IL-17+cells and the level of IL-23R mRNA show increases in the serum of patients with pemphigus foliaceus, in contrast to showing decreases in newly diagnosed patients with pemphigus vulgaris. This may be a result of the Th17 cells have plasticity and converting to Th1-like Th17 cells. There are some reports that the frequency of Th17 cells and level of IL-17 show decreases in other autoimmune and inflammatory diseases, such as lipopolysaccharides responsive beige-like anchor protein deficiency.

Systemic Sclerosis

The imbalance and dysfunction of Th17/Treg cells are crucial to the generation of SSc. Quantitative analysis of Th17 cytokines in lesional skin of SSc showed that the expression of IL-17A, IL-13, IL-22, and IL-26 mRNA are higher compared with healthy control. The levels of circulating Th17 cells and IL-17 elevated in serum of patients with SSc. They are in correlation with disease severity and collagen overproduction. The elevated levels of IL-17A act on dermal vascular smooth muscle cells to promote vascular fibrosis in the patients with SSc, via activating extracellular signal-regulated kinase 1/2 signaling pathway.

Conclusion

In summary, the Th17/IL-17 axis has been identified as a key factor in skin inflammatory diseases, such as psoriasis, HS, AD, PRP, pemphigus, and SSc. Neutralizing IL-17 or IL-23 in psoriasis, HS and PRP has shown promising clinical improvements. Additional studies are required to identify whether IL-17 is involved in the pathogenesis of AA, PRP, pemphigus, and SSc, which may lead to the development of targeted strategies for efficiently ameliorating or specifically eliminating these debilitating diseases.

Author Contributions

TL, YL, JQ, and HF contributed to conception, literature search, and manuscript writing. SL, SY, ST, and YD created graphical illustrations. TL, JQ, and HF contributed to manuscript revision and read the submitted version. All authors contributed to the article and approved the submitted version.

Funding

This work was supported by the National Natural Science Foundation of China (81972931 to HF), the Medical and Health Science and Technology Project of Health Commission of Zhejiang Province (2020KY558 to JQ), and the Zhejiang Provincial Natural Science Foundation (LY20H110001 to YL).

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References 173

  1. 1.

    Rouvier E Luciani MF Mattéi MG Denizot F Golstein P CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol (1993 ) 150(12):5445–56.

    Not in our library

  2. 2.

    Zhou J An X Dong J Wang Y Zhong H Duan L IL-17 induces cellular stress microenvironment of melanocytes to promote autophagic cell apoptosis in vitiligo. FASEB J (2018 ) 32(9):4899–916.

    Not in our library10.1096/fj.201701242rr

  3. 3.

    Zepp JA Zhao J Liu C Bulek K Wu L Chen X IL-17A-Induced PLET1 Expression Contributes to Tissue Repair and Colon Tumorigenesis. J Immunol (2017 ) 199(11):3849–57.

    Not in our library10.4049/jimmunol.1601540

  4. 4.

    Burstein VL Guasconi L Beccacece I Theumer MG Mena C Prinz I IL-17-Mediated Immunity Controls Skin Infection and T Helper 1 Response during Experimental Microsporum canis Dermatophytosis. J Invest Dermatol (2018 ) 138(8):1744–53.

    Not in our library10.1016/j.jid.2018.02.042

  5. 5.

    Park H Li Z Yang XO Chang SH Nurieva R Wang YH A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol (2005 ) 6(11):1133–41.

    Not in our library10.1038/ni1261

  6. 6.
    IL-1-IL-17 Signaling Axis Contributes to Fibrosis and Inflammation in Two Different Murine Models of Systemic Sclerosis · 2018
    Not checked
  7. 7.

    Johnston A Fritz Y Dawes SM Diaconu D Al-Attar PM Guzman AM Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation. J Immunol (2013 ) 190(5):2252–62.

    Not in our library10.4049/jimmunol.1201505

  8. 8.

    Karbach S Croxford AL Oelze M Schüler R Minwegen D Wegner J Interleukin 17 drives vascular inflammation, endothelial dysfunction, and arterial hypertension in psoriasis-like skin disease. Arterioscler Thromb Vasc Biol (2014 ) 34(12):2658–68.

    Not in our library10.1161/atvbaha.114.304108

  9. 9.

    Senra L Mylonas A Kavanagh RD Fallon PG Conrad C Borowczyk-Michalowska J IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation. J Invest Dermatol (2019 ) 139(8):1732–42.e17.

    Not in our library10.1016/j.jid.2019.01.021

  10. 10.

    Uluçkan Ö Jimenez M Karbach S Jeschke A Graña O Keller J Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts. Sci Transl Med (2016 ) 8(330):330ra37.

    Not in our library10.1126/scitranslmed.aad8996

  11. 11.

    Moos S Mohebiany AN Waisman A Kurschus FC Imiquimod-Induced Psoriasis in Mice Depends on the IL-17 Signaling of Keratinocytes. J Invest Dermatol (2019 ) 139(5):1110–7.

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

  12. 12.

    Su Y Huang J Zhao X Lu H Wang W Yang XO Interleukin-17 receptor D constitutes an alternative receptor for interleukin-17A important in psoriasis-like skin inflammation. Sci Immunol (2019 ) 4(36).

    Not in our library10.1126/sciimmunol.aau9657

  13. 13.

    Fujino S Andoh A Bamba S Ogawa A Hata K Araki Y Increased expression of interleukin 17 in inflammatory bowel disease. Gut (2003 ) 52(1):65–70.

    Not in our library10.1136/gut.52.1.65

  14. 14.

    Wu NL Huang DY Tsou HN Lin YC Lin WW Syk mediates IL-17-induced CCL20 expression by targeting Act1-dependent K63-linked ubiquitination of TRAF6. J Invest Dermatol (2015 ) 135(2):490–8.

    Not in our library10.1038/jid.2014.383

  15. 15.

    Nesmond S Muller C Le Naour R Viguier M Bernard P Antonicelli F Characteristic Pattern of IL-17RA, IL-17RB, and IL-17RC in Monocytes/Macrophages and Mast Cells From Patients With Bullous Pemphigoid. Front Immunol (2019 ) 10:2107.

    Not in our library10.3389/fimmu.2019.02107

  16. 16.

    Koenders MI Kolls JK Oppers-Walgreen B van den Bersselaar L Joosten LA Schurr JR Interleukin-17 receptor deficiency results in impaired synovial expression of interleukin-1 and matrix metalloproteinases 3, 9, and 13 and prevents cartilage destruction during chronic reactivated streptococcal cell wall-induced arthritis. Arthritis Rheum (2005 ) 52(10):3239–47.

    Not in our library10.1002/art.21342

  17. 17.

    Xiao X Shi X Fan Y Wu C Zhang X Minze L The Costimulatory Receptor OX40 Inhibits Interleukin-17 Expression through Activation of Repressive Chromatin Remodeling Pathways. Immunity (2016 ) 44(6):1271–83.

    Not in our library10.1016/j.immuni.2016.05.013

  18. 18.

    Jandus C Bioley G Rivals JP Dudler J Speiser D Romero P Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum (2008 ) 58(8):2307–17.

    Not in our library10.1002/art.23655

  19. 19.

    Moran B Sweeney CM Hughes R Malara A Kirthi S Tobin AM Hidradenitis Suppurativa Is Characterized by Dysregulation of the Th17:Treg Cell Axis, Which Is Corrected by Anti-TNF Therapy. J Invest Dermatol (2017 ) 137(11):2389–95.

    Not in our library10.1016/j.jid.2017.05.033

  20. 20.

    Langrish CL Chen Y Blumenschein WM Mattson J Basham B Sedgwick JD IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med (2005 ) 201(2):233–40.

    Not in our library10.1084/jem.20041257

  21. 21.
    RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients · 2019
    No notice
  22. 22.
    Tiam1/Rac1 complex controls Il17a transcription and autoimmunity · 2016
    Not checked
  23. 23.
    Hectd3 promotes pathogenic Th17 lineage through Stat3 activation and Malt1 signaling in neuroinflammation · 2019
    Not checked
  24. 24.

    Goepfert A Lehmann S Blank J Kolbinger F Rondeau J-M Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling. Immunity (2020 ) 52(3):499–512.

    Not in our library10.1016/j.immuni.2020.02.004

  25. 25.

    Ho AW Shen F Conti HR Patel N Childs EE Peterson AC IL-17RC is required for immune signaling via an extended SEF/IL-17R signaling domain in the cytoplasmic tail. J Immunol (2010 ) 185(2):1063–70.

    Not in our library10.4049/jimmunol.0903739

  26. 26.

    Onishi RM Park SJ Hanel W Ho AW Maitra A Gaffen SL SEF/IL-17R (SEFIR) is not enough: an extended SEFIR domain is required for il-17RA-mediated signal transduction. J Biol Chem (2010 ) 285(43):32751–9.

    Not in our library10.1074/jbc.m110.121418

  27. 27.

    Zhang B Liu C Qian W Han Y Li X Deng J Structure of the unique SEFIR domain from human interleukin 17 receptor A reveals a composite ligand-binding site containing a conserved alpha-helix for Act1 binding and IL-17 signaling. Acta Crystallogr D Biol Crystallogr (2014 ) 70(Pt 5):1476–83.

    Not in our library10.1107/s1399004714005227

  28. 28.

    Qian Y Liu C Hartupee J Altuntas CZ Gulen MF Jane-Wit D The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol (2007 ) 8(3):247–56.

    Not in our library10.1038/ni1439

  29. 29.

    Patel DN King CA Bailey SR Holt JW Venkatachalam K Agrawal A Interleukin-17 stimulates C-reactive protein expression in hepatocytes and smooth muscle cells via p38 MAPK and ERK1/2-dependent NF-kappaB and C/EBPbeta activation. J Biol Chem (2007 ) 282(37):27229–38.

    Not in our library10.1074/jbc.m703250200

  30. 30.

    Chang SH Park H Dong C Act1 adaptor protein is an immediate and essential signaling component of interleukin-17 receptor. J Biol Chem (2006 ) 281(47):35603–7.

    Not in our library10.1074/jbc.c600256200

  31. 31.

    Bulek K Liu C Swaidani S Wang L Page RC Gulen MF The inducible kinase IKKi is required for IL-17-dependent signaling associated with neutrophilia and pulmonary inflammation. Nat Immunol (2011 ) 12(9):844–52.

    Not in our library10.1038/ni.2080

  32. 32.

    Wu L Chen X Zhao J Martin B Zepp JA Ko JS A novel IL-17 signaling pathway controlling keratinocyte proliferation and tumorigenesis via the TRAF4-ERK5 axis. J Exp Med (2015 ) 212(10):1571–87.

    Not in our library10.1084/jem.20150204

  33. 33.

    Sun D Novotny M Bulek K Liu C Li X Hamilton T Treatment with IL-17 prolongs the half-life of chemokine CXCL1 mRNA via the adaptor TRAF5 and the splicing-regulatory factor SF2 (ASF). Nat Immunol (2011 ) 12(9):853–60.

    Not in our library10.1038/ni.2081

  34. 34.

    Zhu S Pan W Shi P Gao H Zhao F Song X Modulation of experimental autoimmune encephalomyelitis through TRAF3-mediated suppression of interleukin 17 receptor signaling. J Exp Med (2010 ) 207(12):2647–62.

    Not in our library10.1084/jem.20100703

  35. 35.

    Garg AV Ahmed M Vallejo AN Ma A Gaffen SL The deubiquitinase A20 mediates feedback inhibition of interleukin-17 receptor signaling. Sci Signal (2013 ) 6(278):ra44.

    Not in our library10.1126/scisignal.2003699

  36. 36.

    Chiricozzi A Suarez-Farinas M Fuentes-Duculan J Cueto I Li K Tian S Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris. Br J Dermatol (2016 ) 174(1):136–45.

    Not in our library10.1111/bjd.14034

  37. 37.

    Takahashi H Tsuji H Hashimoto Y Ishida-Yamamoto A Iizuka H Serum cytokines and growth factor levels in Japanese patients with psoriasis. Clin Exp Dermatol (2010 ) 35(6):645–9.

    Not in our library10.1111/j.1365-2230.2009.03704.x

  38. 38.

    Harper EG Guo C Rizzo H Lillis JV Kurtz SE Skorcheva I Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J Invest Dermatol (2009 ) 129(9):2175–83.

    Not in our library10.1038/jid.2009.65

  39. 39.

    Johansen C Usher PA Kjellerup RB Lundsgaard D Iversen L Kragballe K Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Br J Dermatol (2009 ) 160(2):319–24.

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

  40. 40.

    Kolbinger F Loesche C Valentin MA Jiang X Cheng Y Jarvis P β-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis. J Allergy Clin Immunol (2017 ) 139(3):923–32.e8.

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

  41. 41.

    Dyring-Andersen B Honoré TV Madelung A Bzorek M Simonsen S Clemmensen SN Interleukin (IL)-17A and IL-22-producing neutrophils in psoriatic skin. Br J Dermatol (2017 ) 177(6):e321–e2.

    Not in our library10.1111/bjd.15533

  42. 42.

    Cua DJ Tato CM Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol (2010 ) 10(7):479–89.

    Not in our library10.1038/nri2800

  43. 43.

    Mashiko S Bouguermouh S Rubio M Baba N Bissonnette R Sarfati M Human mast cells are major IL-22 producers in patients with psoriasis and atopic dermatitis. J Allergy Clin Immunol (2015 ) 136(2):351–9.e1.

    Not in our library10.1016/j.jaci.2015.01.033

  44. 44.

    Brembilla NC Stalder R Senra L Boehncke WH IL-17A localizes in the exocytic compartment of mast cells in psoriatic skin. Br J Dermatol (2017 ) 177(5):1458–60.

    Not in our library10.1111/bjd.15358

  45. 45.
    Overrepresentation of IL-17A and IL-22 Producing CD8 T Cells in Lesional Skin Suggests Their Involvement in the Pathogenesis of Psoriasis · 2010
    No notice
  46. 46.

    Ueyama A Imura C Fusamae Y Tsujii K Furue Y Aoki M Potential role of IL-17-producing CD4/CD8 double negative alphabeta T cells in psoriatic skin inflammation in a TPA-induced STAT3C transgenic mouse model. J Dermatol Sci (2017 ) 85(1):27–35.

    Not in our library10.1016/j.jdermsci.2016.10.007

  47. 47.

    Cai Y Shen X Ding C Qi C Li K Li X Pivotal role of dermal IL-17-producing gammadelta T cells in skin inflammation. Immunity (2011 ) 35(4):596–610.

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

  48. 48.

    Bernink JH Ohne Y Teunissen MBM Wang J Wu J Krabbendam L c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies. Nat Immunol (2019 ) 20(8):992–1003.

    Not in our library10.1038/s41590-019-0423-0

  49. 49.

    Teunissen MBM Munneke JM Bernink JH Spuls PI Res PCM Te Velde A Composition of innate lymphoid cell subsets in the human skin: enrichment of NCR(+) ILC3 in lesional skin and blood of psoriasis patients. J Invest Dermatol (2014 ) 134(9):2351–60.

    Not in our library10.1038/jid.2014.146

  50. 50.

    Lande R Botti E Jandus C Dojcinovic D Fanelli G Conrad C The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun (2014 ) 5:5621.

    Not in our library10.1038/ncomms6621

  51. 51.

    Tsoi LC Spain SL Ellinghaus E Stuart PE Capon F Knight J Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci. Nat Commun (2015 ) 6:7001.

    Not in our library10.1038/ncomms8001

  52. 52.

    Arakawa A Siewert K Stohr J Besgen P Kim SM Ruhl G Melanocyte antigen triggers autoimmunity in human psoriasis. J Exp Med (2015 ) 212(13):2203–12.

    Not in our library10.1084/jem.20151093

  53. 53.

    Wang M Zhang S Zheng G Huang J Songyang Z Zhao X Gain-of-Function Mutation of Card14 Leads to Spontaneous Psoriasis-like Skin Inflammation through Enhanced Keratinocyte Response to IL-17A. Immunity (2018 ) 49(1):66–79.e5.

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

  54. 54.

    Lande R Gregorio J Facchinetti V Chatterjee B Wang YH Homey B Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature (2007 ) 449(7162):564–9.

    Not in our library10.1038/nature06116

  55. 55.

    Ganguly D Chamilos G Lande R Gregorio J Meller S Facchinetti V Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med (2009 ) 206(9):1983–94.

    Not in our library10.1084/jem.20090480

  56. 56.
    RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients · 2019
    No notice
  57. 57.

    Zheng Y Danilenko DM Valdez P Kasman I Eastham-Anderson J Wu J Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature (2007 ) 445(7128):648–51.

    Not in our library10.1038/nature05505

  58. 58.

    Shimizu T Kamata M Fukaya S Hayashi K Fukuyasu A Tanaka T Anti-IL-17A and IL-23p19 antibodies but not anti-TNFα antibody induce expansion of regulatory T cells and restoration of their suppressive function in imiquimod-induced psoriasiform dermatitis. J Dermatol Sci (2019 ) 95(3):90–8.

    Not in our library10.1016/j.jdermsci.2019.07.006

  59. 59.

    Frischknecht L Vecellio M Selmi C The role of epigenetics and immunological imbalance in the etiopathogenesis of psoriasis and psoriatic arthritis. Ther Adv Musculoskelet Dis (2019 ) 11:1759720x19886505.

    Not in our library10.1177/1759720x19886505

  60. 60.

    Song X Dai D He X Zhu S Yao Y Gao H Growth Factor FGF2 Cooperates with Interleukin-17 to Repair Intestinal Epithelial Damage. Immunity (2015 ) 43(3):488–501.

    Not in our library10.1016/j.immuni.2015.06.024

  61. 61.
    IL-17-producing γδ T cells enhance bone regeneration · 2016
    No notice
  62. 62.

    Lou F Sun Y Xu Z Niu L Wang Z Deng S Excessive Polyamine Generation in Keratinocytes Promotes Self-RNA Sensing by Dendritic Cells in Psoriasis. Immunity (2020 ) 53(1):204–16.e10.

    Not in our library10.1016/j.immuni.2020.06.004

  63. 63.
    Heterogeneous expression pattern of interleukin 17A (IL-17A), IL-17F and their receptors in synovium of rheumatoid arthritis, psoriatic arthritis and osteoarthritis: possible explanation for nonresponse to anti-IL-17 therapy? · 2014
    No notice
  64. 64.

    Raychaudhuri SP Raychaudhuri SK Genovese MC IL-17 receptor and its functional significance in psoriatic arthritis. Mol Cell Biochem (2012 ) 359(1-2):419–29.

    Not in our library10.1007/s11010-011-1036-6

  65. 65.

    Belasco J Louie JS Gulati N Wei N Nograles K Fuentes-Duculan J Comparative genomic profiling of synovium versus skin lesions in psoriatic arthritis. Arthritis Rheumatol (2015 ) 67(4):934–44.

    Not in our library10.1002/art.38995

  66. 66.

    Noordenbos T Yeremenko N Gofita I van de Sande M Tak PP Caňete JD Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis. Arthritis Rheum (2012 ) 64(1):99–109.

    Not in our library10.1002/art.33396

  67. 67.

    Adamopoulos IE Suzuki E Chao CC Gorman D Adda S Maverakis E IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis. Ann Rheum Dis (2015 ) 74(6):1284–92.

    Not in our library10.1136/annrheumdis-2013-204782

  68. 68.

    Wan MT Shin DB Hubbard RA Noe MH Mehta NN Gelfand JM Psoriasis and the risk of diabetes: A prospective population-based cohort study. J Am Acad Dermatol (2018 ) 78(2):315–22.e1.

    Not in our library10.1016/j.jaad.2017.10.050

  69. 69.

    Egeberg A Gisondi P Carrascosa JM Warren RB Mrowietz U The role of the interleukin-23/Th17 pathway in cardiometabolic comorbidity associated with psoriasis. J Eur Acad Dermatol Venereol (2020 ) 34(8):1695–706.

    Not in our library10.1111/jdv.16273

  70. 70.

    Xu M Lu H Lee YH Wu Y Liu K Shi Y An Interleukin-25-Mediated Autoregulatory Circuit in Keratinocytes Plays a Pivotal Role in Psoriatic Skin Inflammation. Immunity (2018 ) 48(4):787–98.e4.

    Not in our library10.1016/j.immuni.2018.03.019

  71. 71.

    Glatt S Baeten D Baker T Griffiths M Ionescu L Lawson ADG Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomised placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation. Ann Rheum Dis (2018 ) 77(4):523–32.

    Not in our library10.1136/annrheumdis-2017-212127

  72. 72.

    Vandeghinste N Klattig J Jagerschmidt C Lavazais S Marsais F Haas JD Neutralization of IL-17C Reduces Skin Inflammation in Mouse Models of Psoriasis and Atopic Dermatitis. J Invest Dermatol (2018 ) 138(7):1555–63.

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

  73. 73.

    Senra L Stalder R Alvarez Martinez D Chizzolini C Boehncke WH Brembilla NC Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis. J Invest Dermatol (2016 ) 136(10):1970–80.

    Not in our library10.1016/j.jid.2016.06.009

  74. 74.

    Wright JF Guo Y Quazi A Luxenberg DP Bennett F Ross JF Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells. J Biol Chem (2007 ) 282(18):13447–55.

    Not in our library10.1074/jbc.m700499200

  75. 75.

    Reich K Sullivan J Arenberger P Jazayeri S Mrowietz U Augustin M Secukinumab shows high and sustained efficacy in nail psoriasis: 2.5-year results from the randomized placebo-controlled TRANSFIGURE study. Br J Dermatol (2020 ).

    Not in our library10.1111/bjd.19262

  76. 76.

    Mease PJ McInnes IB Kirkham B Kavanaugh A Rahman P van der Heijde D Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med (2015 ) 373(14):1329–39.

    Not in our library10.1056/nejmoa1412679

  77. 77.

    Langley RG Elewski BE Lebwohl M Reich K Griffiths CE Papp K Secukinumab in plaque psoriasis–results of two phase 3 trials. N Engl J Med (2014 ) 371(4):326–38.

    Not in our library10.1056/nejmoa1314258

  78. 78.

    Bissonnette R Luger T Thaçi D Toth D Lacombe A Xia S Secukinumab demonstrates high sustained efficacy and a favourable safety profile in patients with moderate-to-severe psoriasis through 5 years of treatment (SCULPTURE Extension Study). J Eur Acad Dermatol Venereol (2018 ) 32(9):1507–14.

    Not in our library10.1111/jdv.14878

  79. 79.

    McInnes IB Mease PJ Kirkham B Kavanaugh A Ritchlin CT Rahman P Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet (2015 ) 386(9999):1137–46.

    Not in our library10.1016/s0140-6736(15)61134-5

  80. 80.

    McInnes IB Mease PJ Ritchlin CT Rahman P Gottlieb AB Kirkham B Secukinumab sustains improvement in signs and symptoms of psoriatic arthritis: 2 year results from the phase 3 FUTURE 2 study. Rheumatol (Oxford) (2017 ) 56(11):1993–2003.

    Not in our library10.1093/rheumatology/kex301

  81. 81.

    Kampylafka E d’Oliveira I Linz C Lerchen V Stemmler F Simon D Resolution of synovitis and arrest of catabolic and anabolic bone changes in patients with psoriatic arthritis by IL-17A blockade with secukinumab: results from the prospective PSARTROS study. Arthritis Res Ther (2018 ) 20(1):153.

    Not in our library10.1186/s13075-018-1653-5

  82. 82.

    van der Heijde D Mease PJ Landewé RBM Rahman P Tahir H Singhal A Secukinumab provides sustained low rates of radiographic progression in psoriatic arthritis: 52-week results from a phase 3 study, FUTURE 5. Rheumatol (Oxford) (2020 ) 59(6):1325–34.

    Not in our library10.1093/rheumatology/kez420

  83. 83.

    Leonardi C Maari C Philipp S Goldblum O Zhang L Burkhardt N Maintenance of skin clearance with ixekizumab treatment of psoriasis: Three-year results from the UNCOVER-3 study. J Am Acad Dermatol (2018 ) 79(5):824–30.

    Not in our library10.1016/j.jaad.2018.05.032

  84. 84.

    Blauvelt A Gooderham M Iversen L Ball S Zhang L Agada NO Efficacy and safety of ixekizumab for the treatment of moderate-to-severe plaque psoriasis: Results through 108 weeks of a randomized, controlled phase 3 clinical trial (UNCOVER-3). J Am Acad Dermatol (2017 ) 77(5):855–62.

    Not in our library10.1016/j.jaad.2017.06.153

  85. 85.

    Mease PJ van der Heijde D Ritchlin CT Okada M Cuchacovich RS Shuler CL Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis (2017 ) 76(1):79–87.

    Not in our library10.1136/annrheumdis-2016-209709

  86. 86.

    Nash P Kirkham B Okada M Rahman P Combe B Burmester G-R Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet (2017 ) 389(10086):2317–27.

    Not in our library10.1016/s0140-6736(17)31429-0

  87. 87.

    Gossec L Baraliakos X Kerschbaumer A de Wit M McInnes I Dougados M EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis (2020 ) 79(6):700–12.

    Not in our library10.1136/annrheumdis-2020-217159

  88. 88.

    Tomalin LE Russell CB Garcet S Ewald DA Klekotka P Nirula A Short-term transcriptional response to IL-17 receptor-A antagonism in the treatment of psoriasis. J Allergy Clin Immunol (2020 ) 145(3):922–32.

    Not in our library10.1016/j.jaci.2019.10.041

  89. 89.

    Papp K Menter A Leonardi C Soung J Weiss S Pillai R Long-term efficacy and safety of brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomized phase III trial (AMAGINE-1). Br J Dermatol (2020 ).

    Not in our library10.1111/bjd.19132

  90. 90.

    Papp KA Reich K Paul C Blauvelt A Baran W Bolduc C A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol (2016 ) 175(2):273–86.

    Not in our library10.1111/bjd.14493

  91. 91.

    Kimmel G Chima M Kim HJ Bares J Yao CJ Singer G Brodalumab in the treatment of moderate to severe psoriasis in patients when previous anti-interleukin 17A therapies have failed. J Am Acad Dermatol (2019 ) 81(3):857–9.

    Not in our library10.1016/j.jaad.2019.05.007

  92. 92.

    Langley RG Armstrong AW Lebwohl MG Blauvelt A Hsu S Tyring S Efficacy and safety of brodalumab in patients with psoriasis who had inadequate responses to ustekinumab: subgroup analysis of two randomized phase III trials. Br J Dermatol (2019 ) 180(2):306–14.

    Not in our library10.1111/bjd.17318

  93. 93.

    Yamasaki K Nakagawa H Kubo Y Ootaki K Efficacy and safety of brodalumab in patients with generalized pustular psoriasis and psoriatic erythroderma: results from a 52-week, open-label study. Br J Dermatol (2017 ) 176(3):741–51.

    Not in our library10.1111/bjd.14702

  94. 94.

    Blauvelt A Papp KA Merola JF Gottlieb AB Cross N Madden C Bimekizumab for patients with moderate-to-severe plaque psoriasis: 60-week results from BE ABLE 2, a randomized, double-blinded, placebo-controlled phase 2b extension study. J Am Acad Dermatol (2020 ).

    Not in our library10.1016/j.jaad.2020.05.105

  95. 95.

    Papp KA Merola JF Gottlieb AB Griffiths CEM Cross N Peterson L Dual neutralization of both interleukin 17A and interleukin 17F with bimekizumab in patients with psoriasis: Results from BE ABLE 1, a 12-week randomized, double-blinded, placebo-controlled phase 2b trial. J Am Acad Dermatol (2018 ) 79(2):277–86.

    Not in our library10.1016/j.jaad.2018.03.037

  96. 96.

    Ritchlin CT Kavanaugh A Merola JF Schett G Scher JU Warren RB Bimekizumab in patients with active psoriatic arthritis: results from a 48-week, randomised, double-blind, placebo-controlled, dose-ranging phase 2b trial. Lancet (2020 ) 395(10222):427–40.

    Not in our library10.1016/s0140-6736(19)33161-7

  97. 97.

    Genovese MC Mysler E Tomita T Papp KA Salvarani C Schwartzman S Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials. Rheumatol (Oxford) (2020 ).

    Not in our library10.1093/rheumatology/keaa189

  98. 98.

    Puig L Lebwohl M Bachelez H Sobell J Jacobson AA Long-term efficacy and safety of brodalumab in the treatment of psoriasis: 120-week results from the randomized, double-blind, placebo- and active comparator-controlled phase 3 AMAGINE-2 trial. J Am Acad Dermatol (2020 ) 82(2):352–9.

    Not in our library10.1016/j.jaad.2019.05.095

  99. 99.

    Strober B Leonardi C Papp KA Mrowietz U Ohtsuki M Bissonnette R Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis: Etanercept comparisons and integrated data. J Am Acad Dermatol (2017 ) 76(3):432–40.e17.

    Not in our library10.1016/j.jaad.2016.09.026

  100. 100.

    Fowler E Ghamrawi RI Ghiam N Liao W Wu JJ Risk of tuberculosis reactivation during interleukin-17 inhibitor therapy for psoriasis: a systematic review. J Eur Acad Dermatol Venereol (2020 ) 34(7):1449–56.

    Not in our library10.1111/jdv.16254

  101. 101.

    Caldarola G Pirro F Di Stefani A Talamonti M Galluzzo M D’Adamio S Clinical and histopathological characterization of eczematous eruptions occurring in course of anti IL-17 treatment: a case series and review of the literature. Expert Opin Biol Ther (2020 ) 20(6):665–72.

    Not in our library10.1080/14712598.2020.1727439

  102. 102.

    Krueger JG Fretzin S Suárez-Fariñas M Haslett PA Phipps KM Cameron GS IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol (2012 ) 130(1):145–54.e9.

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

  103. 103.

    Napolitano M Megna M Fabbrocini G Nisticò SP Balato N Dastoli S Eczematous eruption during anti-interleukin 17 treatment of psoriasis: an emerging condition. Br J Dermatol (2019 ) 181(3):604–6.

    Not in our library10.1111/bjd.17779

  104. 104.

    Al-Janabi A Foulkes AC Mason K Smith CH Griffiths CEM Warren RB Phenotypic switch to eczema in patients receiving biologics for plaque psoriasis: a systematic review. J Eur Acad Dermatol Venereol (2020 ) 34(7):1440–8.

    Not in our library10.1111/jdv.16246

  105. 105.

    Puel A Cypowyj S Bustamante J Wright JF Liu L Lim HK Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science (2011 ) 332(6025):65–8.

    Not in our library10.1126/science.1200439

  106. 106.

    Kisand K Bøe Wolff AS Podkrajsek KT Tserel L Link M Kisand KV Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J Exp Med (2010 ) 207(2):299–308.

    Not in our library10.1084/jem.20091669

  107. 107.

    Conti HR Bruno VM Childs EE Daugherty S Hunter JP Mengesha BG IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis. Cell Host Microbe (2016 ) 20(5):606–17.

    Not in our library10.1016/j.chom.2016.10.001

  108. 108.

    Meller S Di Domizio J Voo KS Friedrich HC Chamilos G Ganguly D T(H)17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26. Nat Immunol (2015 ) 16(9):970–9.

    Not in our library10.1038/ni.3211

  109. 109.

    Li J Ritelli M Ma CS Rao G Habib T Corvilain E Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-β. Sci Immunol (2019 ) 4(41).

    Not in our library10.1126/sciimmunol.aax7965

  110. 110.

    Saunte DM Mrowietz U Puig L Zachariae C Candida infections in patients with psoriasis and psoriatic arthritis treated with interleukin-17 inhibitors and their practical management. Br J Dermatol (2017 ) 177(1):47–62.

    Not in our library10.1111/bjd.15015

  111. 111.

    Philipp S Menter A Nikkels AF Barber K Landells I Eichenfield LF Ustekinumab for the treatment of moderate-to-severe plaque psoriasis in paediatric patients (≥ 6 to < 12 years of age): efficacy, safety, pharmacokinetic and biomarker results from the open-label CADMUS Jr study. Br J Dermatol (2020 ) 183(4):664–72.

    Not in our library10.1111/bjd.19018

  112. 112.

    Papp KA Langley RG Lebwohl M Krueger GG Szapary P Yeilding N Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet (2008 ) 371(9625):1675–84.

    Not in our library10.1016/s0140-6736(08)60726-6

  113. 113.

    Leonardi CL Kimball AB Papp KA Yeilding N Guzzo C Wang Y Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet (2008 ) 371(9625):1665–74.

    Not in our library10.1016/s0140-6736(08)60725-4

  114. 114.

    Gelfand JM Shin DB Alavi A Torigian DA Werner T Papadopoulos M Randomized, Double-Blind, Placebo-Controlled Crossover Study of the Effects of Ustekinumab on Vascular Inflammation in Psoriasis (the VIP-U Trial). J Invest Dermatol (2020 ) 140(1):85–93.e2.

    Not in our library10.1016/j.jid.2019.07.679

  115. 115.

    Kim BS Lee WK Pak K Han J Kim GW Kim HS Ustekinumab treatment is associated with decreased systemic and vascular inflammation in patients with moderate-to-severe psoriasis: Feasibility study using (18)F-fluorodeoxyglucose PET/CT. J Am Acad Dermatol (2019 ) 80(5):1322–31.

    Not in our library10.1016/j.jaad.2018.03.011

  116. 116.

    Papp KA Griffiths CE Gordon K Lebwohl M Szapary PO Wasfi Y Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol (2013 ) 168(4):844–54.

    Not in our library10.1111/bjd.12214

  117. 117.

    Papp KA Blauvelt A Bukhalo M Gooderham M Krueger JG Lacour JP Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis. N Engl J Med (2017 ) 376(16):1551–60.

    Not in our library10.1056/nejmoa1607017

  118. 118.

    Gordon KB Strober B Lebwohl M Augustin M Blauvelt A Poulin Y Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet (2018 ) 392(10148):650–61.

    Not in our library10.1016/s0140-6736(18)31713-6

  119. 119.

    Reich K Papp KA Blauvelt A Tyring SK Sinclair R Thaçi D 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(10091):276–88.

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

  120. 120.

    Kimball AB Papp KA Reich K Gooderham M Li Q Cichanowitz N Efficacy and safety of tildrakizumab for plaque psoriasis with continuous dosing, treatment interruption, dose adjustments and switching from etanercept: results from phase III studies. Br J Dermatol (2020 ) 182(6):1359–68.

    Not in our library10.1111/bjd.18484

  121. 121.

    Deodhar A Gottlieb AB Boehncke WH Dong B Wang Y Zhuang Y Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. Lancet (2018 ) 391(10136):2213–24.

    Not in our library10.1016/s0140-6736(18)30952-8

  122. 122.

    Mease PJ Rahman P Gottlieb AB Kollmeier AP Hsia EC Xu XL Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet (2020 ) 395(10230):1126–36.

    Not in our library10.1016/s0140-6736(20)30263-4

  123. 123.

    Deodhar A Helliwell PS Boehncke W-H Kollmeier AP Hsia EC Subramanian RA Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet (2020 ) 395(10230):1115–25.

    Not in our library10.1016/s0140-6736(20)30265-8

  124. 124.

    Thomi R Cazzaniga S Seyed Jafari SM Schlapbach C Hunger RE Association of Hidradenitis Suppurativa With T Helper 1/T Helper 17 Phenotypes: A Semantic Map Analysis. JAMA Dermatol (2018 ) 154(5):592–5.

    Not in our library10.1001/jamadermatol.2018.0141

  125. 125.

    Kelly G Hughes R McGarry T van den Born M Adamzik K Fitzgerald R Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa. Br J Dermatol (2015 ) 173(6):1431–9.

    Not in our library10.1111/bjd.14075

  126. 126.

    Schlapbach C Hanni T Yawalkar N Hunger RE Expression of the IL-23/Th17 pathway in lesions of hidradenitis suppurativa. J Am Acad Dermatol (2011 ) 65(4):790–8.

    Not in our library10.1016/j.jaad.2010.07.010

  127. 127.

    Matusiak L Szczech J Bieniek A Nowicka-Suszko D Szepietowski JC Increased interleukin (IL)-17 serum levels in patients with hidradenitis suppurativa: Implications for treatment with anti-IL-17 agents. J Am Acad Dermatol (2017 ) 76(4):670–5.

    Not in our library10.1016/j.jaad.2016.10.042

  128. 128.

    Wieland CW Vogl T Ordelman A Vloedgraven HG Verwoolde LH Rensen JM Myeloid marker S100A8/A9 and lymphocyte marker, soluble interleukin 2 receptor: biomarkers of hidradenitis suppurativa disease activity? Br J Dermatol (2013 ) 168(6):1252–8.

    Not in our library10.1111/bjd.12234

  129. 129.

    Lima AL Karl I Giner T Poppe H Schmidt M Presser D Keratinocytes and neutrophils are important sources of proinflammatory molecules in hidradenitis suppurativa. Br J Dermatol (2016 ) 174(3):514–21.

    Not in our library10.1111/bjd.14214

  130. 130.

    van der Zee HH de Ruiter L Boer J van den Broecke DG den Hollander JC Laman JD Alterations in leucocyte subsets and histomorphology in normal-appearing perilesional skin and early and chronic hidradenitis suppurativa lesions. Br J Dermatol (2012 ) 166(1):98–106.

    Not in our library10.1111/j.1365-2133.2011.10643.x

  131. 131.

    Le Jan S Plée J Vallerand D Dupont A Delanez E Durlach A Innate immune cell-produced IL-17 sustains inflammation in bullous pemphigoid. J Invest Dermatol (2014 ) 134(12):2908–17.

    Not in our library10.1038/jid.2014.263

  132. 132.

    Prussick L Rothstein B Joshipura D Saraiya A Turkowski Y Abdat R Open-label, investigator-initiated, single-site exploratory trial evaluating secukinumab, an anti-interleukin-17A monoclonal antibody, for patients with moderate-to-severe hidradenitis suppurativa. Br J Dermatol (2019 ) 181(3):609–11.

    Not in our library10.1111/bjd.17822

  133. 133.

    Frew JW Navrazhina K Grand D Sullivan-Whalen M Gilleaudeau P Garcet S The effect of subcutaneous brodalumab on clinical disease activity in hidradenitis suppurativa: An open-label cohort study. J Am Acad Dermatol (2020 ) 83(5):1341–8.

    Not in our library10.1016/j.jaad.2020.05.007

  134. 134.

    Blok JL Li K Brodmerkel C Horvátovich P Jonkman MF Horváth B Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum. Br J Dermatol (2016 ) 174(4):839–46.

    Not in our library10.1111/bjd.14338

  135. 135.

    Nograles KE Zaba LC Shemer A Fuentes-Duculan J Cardinale I Kikuchi T IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol (2009 ) 123(6):1244–52.e2.

    Not in our library10.1016/j.jaci.2009.03.041

  136. 136.

    Guttman-Yassky E Suárez-Fariñas M Chiricozzi A Nograles KE Shemer A Fuentes-Duculan J Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis. J Allergy Clin Immunol (2009 ) 124(6):1235–44.e58.

    Not in our library10.1016/j.jaci.2009.09.031

  137. 137.

    Noda S Suárez-Fariñas M Ungar B Kim SJ de Guzman Strong C Xu H The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol (2015 ) 136(5):1254–64.

    Not in our library10.1016/j.jaci.2015.08.015

  138. 138.

    Czarnowicki T He H Canter T Han J Lefferdink R Erickson T Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood. J Allergy Clin Immunol (2020 ) 145(1):215–28.

    Not in our library10.1016/j.jaci.2019.09.031

  139. 139.

    Gittler JK Shemer A Suárez-Fariñas M Fuentes-Duculan J Gulewicz KJ Wang CQ Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol (2012 ) 130(6):1344–54.

    Not in our library10.1016/j.jaci.2012.07.012

  140. 140.

    Suárez-Fariñas M Dhingra N Gittler J Shemer A Cardinale I de Guzman Strong C Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol (2013 ) 132(2):361–70.

    Not in our library10.1016/j.jaci.2013.04.046

  141. 141.

    Aktar MK Kido-Nakahara M Furue M Nakahara T Mutual upregulation of endothelin-1 and IL-25 in atopic dermatitis. Allergy (2015 ) 70(7):846–54.

    Not in our library10.1111/all.12633

  142. 142.

    Oyoshi MK Murphy GF Geha RS Filaggrin-deficient mice exhibit TH17-dominated skin inflammation and permissiveness to epicutaneous sensitization with protein antigen. J Allergy Clin Immunol (2009 ) 124(3):485–93, 93 e1.

    Not in our library10.1016/j.jaci.2009.05.042

  143. 143.

    Gutowska-Owsiak D Schaupp AL Salimi M Selvakumar TA McPherson T Taylor S IL-17 downregulates filaggrin and affects keratinocyte expression of genes associated with cellular adhesion. Exp Dermatol (2012 ) 21(2):104–10.

    Not in our library10.1111/j.1600-0625.2011.01412.x

  144. 144.

    Hvid M Vestergaard C Kemp K Christensen GB Deleuran B Deleuran M IL-25 in atopic dermatitis: a possible link between inflammation and skin barrier dysfunction? J Invest Dermatol (2011 ) 131(1):150–7.

    Not in our library10.1038/jid.2010.277

  145. 145.

    Salimi M Barlow JL Saunders SP Xue L Gutowska-Owsiak D Wang X A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J Exp Med (2013 ) 210(13):2939–50.

    Not in our library10.1084/jem.20130351

  146. 146.

    Ungar B Pavel AB Li R Kimmel G Nia J Hashim P Phase 2 randomized, double-blind study of IL-17 targeting with secukinumab in atopic dermatitis. J Allergy Clin Immunol (2020 ).

    Not in our library10.1016/j.jaci.2020.04.055

  147. 147.

    Pan Y Xu L Qiao J Fang H A systematic review of ustekinumab in the treatment of atopic dermatitis. J Dermatolog Treat (2018 ) 29(6):539–41.

    Not in our library10.1080/09546634.2017.1406894

  148. 148.

    Khattri S Brunner PM Garcet S Finney R Cohen SR Oliva M Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis. Exp Dermatol (2017 ) 26(1):28–35.

    Not in our library10.1111/exd.13112

  149. 149.

    Saeki H Kabashima K Tokura Y Murata Y Shiraishi A Tamamura R Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase II study. Br J Dermatol (2017 ) 177(2):419–27.

    Not in our library10.1111/bjd.15493

  150. 150.

    Garzorz N Alsisi M Todorova A Atenhan A Thomas J Lauffer F Dissecting susceptibility from exogenous triggers: the model of alopecia areata and associated inflammatory skin diseases. J Eur Acad Dermatol Venereol (2015 ) 29(12):2429–35.

    Not in our library10.1111/jdv.13325

  151. 151.

    Atwa MA Youssef N Bayoumy NM. T-helper 17 cytokines (interleukins 17, 21, 22, and 6, and tumor necrosis factor-α) in patients with alopecia areata: association with clinical type and severity. Int J Dermatol (2016 ) 55(6):666–72.

    Not in our library10.1111/ijd.12808

  152. 152.

    Tembhre MK Sharma VK T-helper and regulatory T-cell cytokines in the peripheral blood of patients with active alopecia areata. Br J Dermatol (2013 ) 169(3):543–8.

    Not in our library10.1111/bjd.12396

  153. 153.

    Han YM Sheng YY Xu F Qi SS Liu XJ Hu RM Imbalance of T-helper 17 and regulatory T cells in patients with alopecia areata. J Dermatol (2015 ) 42(10):981–8.

    Not in our library10.1111/1346-8138.12978

  154. 154.

    Loh SH Moon HN Lew BL Sim WY Role of T helper 17 cells and T regulatory cells in alopecia areata: comparison of lesion and serum cytokine between controls and patients. J Eur Acad Dermatol Venereol (2018 ) 32(6):1028–33.

    Not in our library10.1111/jdv.14775

  155. 155.

    Ortolan LS Kim SR Crotts S Liu LY Craiglow BG Wambier C IL-12/IL-23 neutralization is ineffective for alopecia areata in mice and humans. J Allergy Clin Immunol (2019 ) 144(6):1731–4.e1.

    Not in our library10.1016/j.jaci.2019.08.014

  156. 156.

    Guttman-Yassky E Nia JK Hashim PW Mansouri Y Alia E Taliercio M Efficacy and safety of secukinumab treatment in adults with extensive alopecia areata. Arch Dermatol Res (2018 ) 310(8):607–14.

    Not in our library10.1007/s00403-018-1853-5

  157. 157.

    Feldmeyer L Mylonas A Demaria O Mennella A Yawalkar N Laffitte E Interleukin 23-Helper T Cell 17 Axis as a Treatment Target for Pityriasis Rubra Pilaris. JAMA Dermatol (2017 ) 153(4):304–8.

    Not in our library10.1001/jamadermatol.2016.5384

  158. 158.

    Napolitano M Abeni D Didona B Biologics for pityriasis rubra pilaris treatment: A review of the literature. J Am Acad Dermatol (2018 ) 79(2):353–9.e11.

    Not in our library10.1016/j.jaad.2018.03.036

  159. 159.

    Schuster D Pfister-Wartha A Bruckner-Tuderman L Schempp CM Successful Treatment of Refractory Pityriasis Rubra Pilaris With Secukinumab. JAMA Dermatol (2016 ) 152(11):1278–80.

    Not in our library10.1001/jamadermatol.2016.3885

  160. 160.

    Haynes D Strunck JL Topham CA Ortega-Loayza AG Kent G Cassidy PB Evaluation of Ixekizumab Treatment for Patients With Pityriasis Rubra Pilaris: A Single-Arm Trial. JAMA Dermatol (2020 ) 156(6):668–75.

    Not in our library10.1001/jamadermatol.2020.0932

  161. 161.

    Napolitano M Lembo L Fania L Abeni D Didona D Didona B Ustekinumab treatment of pityriasis rubra pilaris: A report of five cases. J Dermatol (2018 ) 45(2):202–6.

    Not in our library10.1111/1346-8138.14114

  162. 162.

    Xue J Su W Chen Z Ke Y Du X Zhou Q Overexpression of interleukin-23 and interleukin-17 in the lesion of pemphigus vulgaris: a preliminary study. Mediators Inflamm (2014 ) 2014:463928.

    Not in our library10.1155/2014/463928

  163. 163.

    Timoteo RP da Silva MV Miguel CB Silva DA Catarino JD Rodrigues Junior V Th1/Th17-Related Cytokines and Chemokines and Their Implications in the Pathogenesis of Pemphigus Vulgaris. Mediators Inflamm (2017 ) 2017:7151285.

    Not in our library10.1155/2017/7151285

  164. 164.

    Ben Jmaa M Abida O Fakhfakh R Bahloul E Sellami K Gaddour L Involvement of the IL23/Th17 Pathway in the Pathogenesis of Tunisian Pemphigus Foliaceus. Mediators Inflamm (2018 ) 2018:8206983.

    Not in our library10.1155/2018/8206983

  165. 165.

    Gholibeigian Z Izad M Daneshpazhooh M Mortazavi H Salehi Z Behruzifar S Decreased serum levels of interleukin-17, interleukin-23, TGF-β in pemphigus vulgaris patients, and their association with disease phase. Dermatol Ther (2020 ) e14071.

    Not in our library10.1111/dth.14071

  166. 166.

    Kamali AN Noorbakhsh SM Hamedifar H Jadidi-Niaragh F Yazdani R Bautista JM A role for Th1-like Th17 cells in the pathogenesis of inflammatory and autoimmune disorders. Mol Immunol (2019 ) 105:107–15.

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

  167. 167.

    Azizi G Mirshafiey A Abolhassani H Yazdani R Ghanavatinejad A Noorbakhsh F The imbalance of circulating T helper subsets and regulatory T cells in patients with LRBA deficiency: Correlation with disease severity. J Cell Physiol (2018 ) 233(11):8767–77.

    Not in our library10.1002/jcp.26772

  168. 168.

    Mo C Zeng Z Deng Q Ding Y Xiao R Imbalance between T helper 17 and regulatory T cell subsets plays a significant role in the pathogenesis of systemic sclerosis. BioMed Pharmacother (2018 ) 108:177–83.

    Not in our library10.1016/j.biopha.2018.09.037

  169. 169.

    Zhou Y Hou W Xu K Han D Jiang C Mou K The elevated expression of Th17-related cytokines and receptors is associated with skin lesion severity in early systemic sclerosis. Hum Immunol (2015 ) 76(1):22–9.

    Not in our library10.1016/j.humimm.2014.12.008

  170. 170.

    Gonçalves RSG Pereira MC Dantas AT Almeida AR Rego M Lima EA CCL3, IL-7, IL-13 and IFNγ transcripts are increased in skin’s biopsy of systemic sclerosis. Exp Dermatol (2019 ) 28(10):1172–5.

    Not in our library10.1111/exd.13982

  171. 171.
    Serum concentrations of IL-17A, IL-17B, IL-17E and IL-17F in patients with systemic sclerosis · 2019
    Not checked
  172. 172.
    Increased frequency of Th17 cells in systemic sclerosis is related to disease activity and collagen overproduction · 2014
    No notice
  173. 173.

    Liu M Yang J Xing X Cui X Li M Interleukin-17A promotes functional activation of systemic sclerosis patient-derived dermal vascular smooth muscle cells by extracellular-regulated protein kinases signalling pathway. Arthritis Res Ther (2014 ) 16(6):4223.

    Not in our library10.1186/s13075-014-0512-2

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