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Macrophages: friend or foe in idiopathic pulmonary fibrosis?

Lei Zhang, Yi Wang, Guorao Wu and 3 more

Respiratory Research · 2018 · Review

doi:10.1186/s12931-018-0864-2

Abstract

Idiopathic pulmonary fibrosis (IPF) is a prototype of lethal, chronic, progressive interstitial lung disease of unknown etiology. Over the past decade, macrophage has been recognized to play a significant role in IPF pathogenesis. Depending on the local microenvironments, macrophages can be polarized to either classically activated (M1) or alternatively activated (M2) phenotypes. In general, M1 macrophages are responsible for wound healing after alveolar epithelial injury, while M2 macrophages are designated to resolve wound healing processes or terminate inflammatory responses in the lung. IPF is a pathological consequence resulted from altered wound healing in response to persistent lung injury. In this review, we intend to summarize the current state of knowledge regarding the process of macrophage polarization and its mediators in the pathogenesis of pulmonary fibrosis. Our goal is to update the understanding of the mechanisms underlying the initiation and progression of IPF, and by which, we expect to provide help for developing effective therapeutic strategies in clinical settings.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 17, 2026. Paragraph numbers are ours, so an answer can point at one.

Background

Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing lung disease with poor prognosis and no effective treatment. It is characterized by the development of excessive extracellular matrix deposition, leading to decreased static lung compliance, disrupted gas exchange, and ultimately, respiratory failure and death. The median survival time for IPF patients is approximately 3 years after the initial diagnosis. Notably, the incidence of IPF rises dramatically with age and is estimated to be 3–9 cases per 100,000 people in Europe and North America, which is slightly higher than that in Asia and South America.

It is believed that IPF is resulted from a complex interaction between multiple genetic and non-genetic risk factors (e.g., cigarette smoking and infection). However, the relative contribution of genetic and non-genetic risk factors is likely to vary among individuals. Past genetic studies in familial and sporadic IPF patients have characterized that the surfactant-associated genes (surfactant protein C, SFTPC; surfactant protein A2, SFTPA2; and ATP binding cassette member A3, ABCA3) and the telomerase-related genes (telomerase reverse transcriptase, TERT; telomerase RNA component, TERC; and regulator of telomere elongation helicase 1, RTEL1) are associated with IPF susceptibility. More recently, two large genome-wide association studies (GWASs) conducted in patients with sporadic and familiar IPF not only confirmed known associations with TERC, TERT, and mucin 5B gene (MUC5B), but also identified novel risk genes such as the toll interacting protein (TOLLIP) and the signal peptide peptidase like 2C (SPPL2C). Of note, excess matrix accumulation is thought to be an important part in the pathological process of IPF, and its related proteins such as matrix metalloproteinase 1 (MMP1) and matrix metalloproteinase 19 (MMP19) that are strongly upregulated in IPF are proposed to be potential peripheral blood biomarkers. In support of this notion, a frameshift deletion (c.988delG, p.A330fs) in MMP1 and a nonsense mutation (c.T1155A, p.Y385X) in MMP19 were characterized in IPF patients. Although these discoveries are exciting, how non-genetic factors trigger those genetic predisposed individuals to initiate IPF process is unfortunately remained poorly understood, which is not our focus in the current review and will be reviewed elsewhere.

Monocytes/macrophages, which originate from progenitors in the bone marrow, circulate in the peripheral blood or migrate into different tissues and constitute the foremost controllers of both innate and acquired immunity. In general, circulating monocytes leave the blood and migrate into tissues, where they differentiate into macrophages following exposure to different stimuli, including local growth factors, cytokines and microbial debris. Macrophages are critical to antigen removal by phagocytosis and the clearance of microbes, apoptotic cells and neoplastic cells. Furthermore, in activated immune responses, macrophages are an extremely heterogeneous population, exerting a combination of pro-inflammatory and anti-inflammatory functions. Typically, macrophages that mainly produce pro-inflammatory cytokines are called classically activated macrophages (M1), which can be activated either by IFN-γ or lipopolysaccharide (LPS). In contrast, macrophages that attenuate inflammation and encourage wound repair are referred to as alternatively activated macrophages (M2), which can be activated by IL-4 or IL-13. It is believed that enhanced macrophage M2 program is associated with fibrotic remodeling of internal organs, including the heart, kidneys, liver, gastrointestinal tract and lungs. Therefore, in this review, we mainly discuss the current state of knowledge regarding the process of macrophage polarization and its mediators in the pathogenesis of pulmonary fibrosis. Our goal is to update the understanding of the mechanisms underlying the initiation and progression of IPF, and by which, we expect to provide help for developing effective therapeutic strategies in clinical settings.

Origin of macrophages

Macrophages are small populations of leukocytes that play an important role in the cross-talk between innate and adaptive immunity. As early as 1893, Metchnikoff first described the term “phagocytes” when he used a rose thorn to challenge a starfish. He classified the phagocytes into macrophages (macro = big, phage = eater) and microphages (now better known as neutrophils), which promoted the development of a theory of phagocytosis. In the 1960s, several studies proposed that macrophages were solely derived from the terminal differentiation of circulating monocytes. However, this theory has been refuted by the recent discoveries that most adult tissue-resident macrophages are seeded before birth, stem from the embryonal yolk sac and fetal liver, possess a self-renewing capacity and are maintained independent of circulating monocytes. In addition, the function of macrophages varies significantly based on their anatomical location, functional phenotype, morphology, as well as their gene expression profile, such as the alveolar macrophages, adipose tissue macrophages, Kupffer cells in the liver, and microglia cells in the central nervous system.

Pulmonary macrophages

Pulmonary macrophage populations are classified into two main categories: alveolar macrophages (AMs), which strategically reside in the alveoli, and interstitial macrophages (IMs), which are located within the lung parenchymal tissue. Given the fact that previous studies in macrophages were conducted in animals or human mononuclear phagocytes from blood and small tissue resections around tumors, Desch and colleagues recently collected pulmonary mononuclear phagocytes from fully intact non-diseased human lungs and identified five extravascular macrophage phagocytes based on phenotype, location, and gene expression, supporting the growing approval of myeloid cell diversity in tissues. It is now clear that AMs colonize the lung tissues shortly after birth and display remarkable self-renewal properties independent of blood monocyte input in the steady-state. In contrast, IMs are less well studied. Scott et al. demonstrated that the IM compartment contains cells derived from both yolk-sac macrophages and bone marrow-derived monocytes (BMDMs). However, the contribution of BMDMs to this population is still under investigation. Functionally, AMs are the chief effector cells of immune responses and have both proinflammatory and anti-inflammatory properties, whereas IMs play a major role in maintaining immune homeostasis in the respiratory tract and inducing immune tolerance to harmless antigens. Currently, a growing body of evidence supports a role for both AMs and IMs in the pathogenesis of pulmonary fibrosis.

Macrophage polarization in IPF

Macrophages are remarkable plastic cells that can transform from one phenotype to another. Macrophage polarization is a dynamic process whereby macrophages manifest different functional phenotypes in response to micro-environmental stimuli and signals. As the most abundant immune cells in the lungs (approximately 70% of the immune cells), macrophages play a vital role in airway remodeling in pulmonary fibrosis. Beyond the AM/IM macrophage subtype delineation, pulmonary macrophages as aforementioned, can be characterized as classically activated macrophages (also termed M1) or alternatively activated macrophages (M2) (Fig. 1). These macrophage subtypes differ in the expression of their cell surface markers, production of specific factors, and biological activities. Both M1 and M2 macrophages have been noted to be involved in the pathogenesis of pulmonary fibrosis, which will be discussed in detail in the following sections.

Classically activated macrophages (M1) and IPF

M1 macrophages contribute to the host defense against pathogens by generating reactive nitric oxide (NO) via inducible nitric oxide synthase (iNOS) and releasing proinflammatory cytokines and chemokines such as IL-1β, IL-12, IL-23, CCL2 and TNF-α. Phenotypically, this cell type is characterized by the expression of high levels of CD80, TLR4, MHCII and CD86. Therefore, M1 macrophages have robust anti-microbial and anti-tumor activities, mediate tissue damage and initiate inflammatory responses. Potent inducers such as LPS, IFN-γ, and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulate the generation of M1 macrophages, from either naïve M0 or polarized M2 macrophages. Other endogenous alarmins such as oxidized low-density lipoprotein, fatty acids, caveolin-1 (Cav-1), and high-mobility group box 1 (HMGB1), are also found to induce M1 biased macrophage polarization. Nevertheless, it still remains unknown whether they exert similar effects on pulmonary fibrosis. Of importantly note, there is evidence that the polarized M1 macrophages can be switched back to the M0 state in a cytokine-deficient medium for 12 days or re-differentiated into another cell phenotype after culture in an alternative polarizing medium.

In the current paradigm of IPF pathogenesis, pulmonary fibrosis progresses as a final pathological outcome of aberrant wound healing responses to persistent lung injury. Pulmonary cellular damage caused by environmental particulates, infection or mechanical damage, often result in the disruption of normal lung architecture, initiating a wound healing response. At the early inflammatory stages, acute lung injury promotes an M1 phenotype under the control of transcription factor interferon regulatory factor 5 (IRF-5) with expression of high levels of iNOS and proinflammatory cytokines,which is associated with Th1 immune responses and responds to IFN-γ and toll-like receptor (TLR) ligands to maximize cytotoxic activity. However, sustained inflammatory responses would serve as a trigger to initiate fibrotic responses in the lung. Indeed, during the course of aberrant wound healing processes, there is an early and sustained enrichment in the numbers of exudate macrophages (ExM) and their precursors, the Ly-6Chigh monocytes. For example, targeted type II alveolar epithelial cell (AEC II) injury induces a modest inflammatory response that is nonetheless significantly enriched for alternatively activated and profibrotic ExM and Ly-6Chigh monocytes. The accumulation of these nonresident cells and the development of pulmonary fibrosis in response to targeted alveolar injury is CCR2 dependent, thereby implicating ExM and Ly-6Chigh monocytes and the CCR2/CCR2-ligand axis as potential therapeutic targets to treat or prevent fibrotic lung disease.

Generally, the LPS/TLR4 pathway has been considered one of the major pathways in M1 macrophage polarization. For example, the LPS/TLR4 pathway activates NF-kB and IRF3 and promotes the secretion of proinflammatory cytokines (e.g., IL-6 and TNF-α) to exacerbate macrophage M1 polarization. This was further supported by studies showing that the LPS/TLR4 activates STAT1 to induce M1 polarization in an MyD88-independent fashion. Interestingly, deletion of both TLR2 and TLR4 increased the susceptibility to bleomycin- and radiation-induced pulmonary fibrosis. Similarly, IL-1R–associated kinase-M (IRAK-M), an MyD88-dependent inhibitor of TLR signaling, suppresses deleterious inflammation but may paradoxically promote fibrogenesis, where IRAK-M was noted to promote macrophage M2 program in the setting of bleomycin-induced lung injury, which drives lung fibrogenesis in an IL-13–dependent fashion. Furthermore, during the evolution of radiation-induced pulmonary fibrosis, patients manifested enhanced mRNA and protein expression of iNOS within the radiation pneumonic stage, whereas the high levels of arginase 1 (Arg 1) expression occurred within the radiation-induced fibrotic phase. Intriguingly, macrophage inflammatory protein-1α (MIP-1α, also known as CCL3) arises mainly from M1, while its chemotactic affinity toward M2 is stronger than it is for M1. The interaction between MIP-1α and macrophages in different activated states may play a crucial role in regulating the transition from radiation pneumonitis to radiation pulmonary fibrosis. It was also noted that TLR2 was elevated in IPF patients, and pharmacologic inhibition of TLR2 protected mice from bleomycin induced lung injury and fibrosis. Similarly, mice with macrophage specific deletion of IRF-5 manifested fibrotic responses in adipose tissue following high-fat diet induction. Collectively, those data indicate that M1 macrophage plays an essential role for wound repair, but it may also serve as a double edged sword to either trigger or prevent fibrotic responses. Nevertheless, the exact extracellular microenvironments relevant to its functional direction (e.g., in favor or against fibrotic responses) are yet to be elucidated.

Alternatively activated macrophages (M2) and IPF

M2 macrophages could be induced by a broad array of mediators such as IL-4, IL-13, TGF-β, and IL-10, and are implicated in the aberrant wound-healing cascade during fibrosis. Depending upon the specific stimulators, M2 macrophages are further subdivided into 3 subgroups, namely, M2a, M2b, and M2c. The M2a subtype is induced by IL-4, IL-13, fungal and helminthic infections. M2b is elicited by IL-1 receptor ligands, immune complexes, and LPS, whereas M2c is activated by IL-10, TGF-β1, and glucocorticoids. More recently, an additional M2 subset, the M2d macrophage, was identified designated by the reduced secretion of IL-12 and enhanced release of IL-10 (Fig. 1). However, there is no unique surface marker to distinguish each subset of M2 macrophages, and they are characterized by low levels of MHCII, CD86, and iNOS2 but high levels of arginase-1, the family proteins chitinase-like Ym1/2 and Fizz1/RELM-α (found in inflammatory zone 1), and cell surface receptors such as macrophage mannose receptor, also called CD206. Analysis of over 72 non-diseased human lungs consistently indicated that CD206 is exclusively expressed on alveolar macrophages rather than on cells found in blood or in the intravascular compartment of the lung, which exerts an important function in the phagocytosis of M2 cells via increasing efferocytosis of invading pathogens and apoptotic cells. In addition, recent studies have indicated that transcription factors and other intracellular proteins, such as tuberous sclerosis complex 1 (TSC1), stress-responsive activating transcription factor 7 (ATF 7), STIP1 homology and U-Box containing protein 1 (STUB1), ten eleven translocation (Tet) methylcytosine dioxygenase (Tet2), microRNA (MiR-511), interferon regulatory factor 4 (IRF4), peroxisome proliferator-activated receptor gamma (PPARγ), and Krueppel-like factor 4 (KLF-4) are also involved in the polarization of M2 macrophages.

During the course of IPF development and progression, the predominant infiltration of M2 macrophages in the areas of lung fibrosis acts as a vital regulator of fibrogenesis. Generally, excessive M2-associated and Th2-driven responses are an important part of many fibrotic diseases. For example, alveolar M2 macrophages, which are located close in proximity to sites of pulmonary injury undergoing repair, release CCL18 to stimulate fibroblast producing collagen. On the other hand, the proximate M2 macrophages bind to collagen type I via β2-integrins and scavenger receptors, thereby further increasing their CCL18 production, which creates a self-perpetuating vicious cycle of augmented, continuous M2 macrophage activation and excessive collagen production by lung fibroblasts. Indeed, upon activation, M2 macrophages can produce profibrotic mediators such as TGF-β and PDGF to induce continuous fibroblast activation and to promote myofibroblast proliferation. Similarly, IL-10 generates a Th2 microenvironment in favor of bleomycin- or helminth-induced lung fibrosis, which involves fibrocyte recruitment and M2 macrophage activation likely through the CCL2/CCR2 axis, leading to excessive extracellular matrix (ECM) deposition along with distorted lung tissue architecture, and ultimately resulting in pulmonary fibrosis and respiratory failure, although the underlying mechanisms are yet to be fully established.

In addition to Th2 cells, eosinophils, innate lymphoid type 2 cells (ILC2s), CD4+CD25+ regulatory T cells (Tregs), and mesenchymal stromal cells (MSCs) were recently reported to drive the polarization of M2 macrophages. For example, mice infused with syngeneic CD4+CD25+ Treg cells have an increased population of CD206+ peritoneal macrophages, with low levels of CD80 and MHCII. Interestingly, Tregs lack of Tim-3 are noted to repress the expression of p-STAT3, thereby attenuating the induction of M2 macrophages in acute respiratory distress syndrome (ARDS)-associated pulmonary fibroproliferation. Similarly, natural killer T cells (NKTs), a subset of T lymphocytes expressing membrane receptors from both T and NK lineages, can mediate a protective effect against fibrosis by inhibiting a Th2 response and preventing M2 macrophage polarization in the bleomycin animal model.

It has been well known that IL-4 is the major inducer for macrophage M2 program by activating its two major downstream signals, JAK1/STAT6 and PI3K/AKT. Indeed, Guo et al. reported that elevated Gab1 and Gab2 regulate IL-4-induced macrophage polarization in bleomycin-induced fibrotic lungs, with Gab1 positively regulating AKT signaling and Gab2 positively regulating STAT6 signaling. Similarly, Kral et al. noted that myeloid PTEN deficiency mice following bleomycin induction manifest sustained PI3K activation to enhance macrophage M2 program, leading to increased morbidity and decreased survival, although these mice exhibit impaired recruitment function. Furthermore, deficiency of shp2, a ubiquitously expressed cytoplasmic tyrosine phosphatase, increases the sensitivity to chitin-induced M2 macrophage polarization and bleomycin-induced pulmonary fibrosis by enhancing IL-4–induced JAK1/STAT6 signaling. Other than cytokines, altered adenosine metabolism was also noted to regulate macrophage M2 program. Adenosine is generated in response to cellular stress and damage, and extracellular accumulation of adenosine and subsequent activation of its receptor, ADORA2B, polarizes macrophages to a fibrotic phenotype. Therefore, mice with macrophage specific deletion of ADORA2B are protected from bleomycin-induced lung injury and fibrosis. It was further noted that hypoxia-inducible factor 1-α (HIF-1α) enhances ADORA2B expression to regulates M2 macrophage differentiation and production of profibrotic mediators.

It is noteworthy that mitochondrial oxidative stress and mitochondrial turnover in alveolar macrophages are directly linked to pulmonary fibrosis, although the exact molecular mechanisms that modulate mitochondrial dynamics are currently not known. The mitochondrial calcium uniporter (MCU) is a highly selective ion channel to transport Ca2+ into the mitochondrial matrix for modulation of cellular metabolism. MCU was recently found to polarize macrophages to a profibrotic phenotype after exposure to asbestos by regulating ATP production. Similarly, mitochondrial Cu,Zn-SOD accelerates the development of pulmonary fibrosis by inducing early and sustained alternative activation of macrophages through redox regulation of the Jumonji domain-containing protein 3 (Jmjd3). Collectively, these data provided convincing evidence that mitochondrial stress also regulates macrophage M2 program implicated in the pathogenesis of pulmonary fibrosis.

Interestingly, there is compelling evidence that endoplasmic reticulum (ER) stress modulates the activation of M2 macrophages. During the past few years, our laboratory has been focused on the effect of ER stress on fibrogenesis. We first demonstrated evidence that pulmonary fibrosis manifests altered C/EBP homologous protein (CHOP) expression and ER stress in both IPF patients and animals with bleomycin-induced pulmonary fibrosis. In consistent with these observations, mice deficient in Chop were protected from bleomycin-induced lung injury and fibrosis. Specifically, the loss of Chop significantly attenuated TGF-β production along with reduced M2 macrophage infiltration in the lung following bleomycin induction. Mechanistic studies revealed that Chop deficiency suppressed the M2 program in macrophages, which then attenuated TGF-β secretion. The loss of Chop enhanced the expression of SOCS1 and SOCS3, thereby inhibiting STAT6/PPARγ signaling that is essential for macrophage M2 program. Similarly, an ovalbumin (OVA)-induced allergic airway inflammatory model revealed that Chop regulates STAT6 phosphorylation, thereby enhancing the expression of mouse transcription factor EC (Tfec), which then transcribes IL-4 receptor a (IL-4Ra) expression to promote M2 program in macrophages. Taken together, those data provide novel insights into the role of ER stress in modulating macrophage M2 program implicated in the pathogenesis of pulmonary fibrosis.

Conclusion

Lung M1 and M2 macrophages are distinct cell subtypes and are both involved in the pathogenesis of pulmonary fibrosis. M1 macrophages express high levels of proinflammatory cytokines, while M2 macrophages express high levels of Th2-type cytokines. Owing to their different cytokine expression profiles, M1 and M2 macrophages play different roles in the pathogenesis of pulmonary fibrosis. Generally, M1 macrophages are responsible for wound healing after alveolar epithelial injury, while M2 macrophages are designated to resolve wound healing processes or terminate inflammatory responses in the lung. IPF is a pathological consequence resulted from altered wound healing in response to persistent lung injury. A variety of regulatory cytokines, chemokines, mediators, and immune-regulatory cells affect polarization and chemotaxis of the lung macrophages (Fig. 2). These mediators interplay and influence disease duration and severity through altered polarization of M1 and M2 cells. Therefore, strategies aimed at modulation of lung macrophage phenotypes may have great potential for prevention and treatment of pulmonary fibrosis in clinical settings.

As noted above, IPF is a hard-to-diagnose fatal interstitial lung disease with a poor response to traditional therapies. Therefore, the development of reliable and fast diagnostic techniques and effective therapies is highly desirable, while targeting the activation and recruitment of M2 macrophages could be a viable therapeutic strategy. Indeed, pirfenidone, one of the two currently US Food and Drug Administration (FDA) approved drugs (pirfenidone and nintedanib) for treatment of human IPF, exerts its anti-fibrotic property in part by suppressing TGF-β expression relevant to macrophage M2 polarization and fibroblast activation. Moreover, neotuberostemonine (NTS), one of the traditional Chinese medicines included in all versions of the Chinese Pharmacopoeia, can effectively attenuate BLM-induced lung fibrosis via suppressing the recruitment and polarization of M2 macrophages. Intriguingly, Ji et al. demonstrated that mineralocorticoid receptor (MR) antagonism by liposome-encapsulated spironolactone (Lipo-SP) could alleviate bleomycin-induced acute pulmonary injury and fibrosis, partially by reducing circulating inflammatory Ly6Chigh monocyte expansion and repressing alternatively activated mononuclear phagocytes in the alveolar compartment.

Although therapies for IPF include a variety of drugs and non-pharmacological interventions, there is still a pressing need for new therapeutic approaches as current therapies are unable to effectively attenuate disease progression or reverse lung fibrosis. Despite past extensive studies, many questions remain unsolved regarding the exact mechanisms of manipulating the balance of M1/M2 phenotype in IPF pathogenesis. Future studies aimed at dissecting the interplay between macrophages and fibroblasts and how macrophages create an extracellular milieu in favor of fibroblast activation and myofibroblast proliferation, would be crucial for developing effective therapies against IPF and other fibrotic diseases.

References 124

  1. 1.

    Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet. 2017;389:1941-1952.

    Not in our library10.1016/s0140-6736(17)30866-8

  2. 2.

    Wilson MS, Wynn TA. Pulmonary fibrosis: pathogenesis, etiology and regulation. Mucosal Immunol. 2009;2:103-121.

    Not in our library10.1038/mi.2008.85

  3. 3.

    Helling BA, Yang IV. Epigenetics in lung fibrosis: from pathobiology to treatment perspective. Curr Opin Pulm Med. 2015;21:454-462.

    Not in our library10.1097/mcp.0000000000000191

  4. 4.

    Hewlett JC, Kropski JA, Blackwell TS. Idiopathic pulmonary fibrosis: epithelial-mesenchymal interactions and emerging therapeutic targets. Matrix Biol. 2018.

    Not in our library10.1016/j.matbio.2018.03.021

  5. 5.

    Zhang L, Wang Y, Pandupuspitasari NS, Wu G, Xiang X, Gong Q, Xiong W, Wang CY, Yang P, Ren B. Endoplasmic reticulum stress, a new wrestler, in the pathogenesis of idiopathic pulmonary fibrosis. Am J Transl Res. 2017;9:722-735.

    Not in our library

  6. 6.

    Kropski JA, Lawson WE, Young LR, Blackwell TS. Genetic studies provide clues on the pathogenesis of idiopathic pulmonary fibrosis. Dis Model Mech. 2013;6:9-17.

    Not in our library10.1242/dmm.010736

  7. 7.

    Hutchinson J, Fogarty A, Hubbard R, McKeever T. Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review. Eur Respir J. 2015;46:795-806.

    Not in our library10.1183/09031936.00185114

  8. 8.

    Hopkins RB, Burke N, Fell C, Dion G, Kolb M. Epidemiology and survival of idiopathic pulmonary fibrosis from national data in Canada. Eur Respir J. 2016;48:187-195.

    Not in our library10.1183/13993003.01504-2015

  9. 9.

    Evans CM, Fingerlin TE, Schwarz MI, Lynch D, Kurche J, Warg L, Yang IV, Schwartz DA. Idiopathic pulmonary fibrosis: a genetic disease that involves Mucociliary dysfunction of the peripheral airways. Physiol Rev. 2016;96:1567-1591.

    Not in our library10.1152/physrev.00004.2016

  10. 10.

    Lawson WE, Grant SW, Ambrosini V, Womble KE, Dawson EP, Lane KB, Markin C, Renzoni E, Lympany P, Thomas AQ, et al. Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF. Thorax. 2004;59:977–80.

    Not in our library10.1136/thx.2004.026336

  11. 11.

    Wang Y, Kuan PJ, Xing C, Cronkhite JT, Torres F, Rosenblatt RL, DiMaio JM, Kinch LN, Grishin NV, Garcia CK. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet. 2009;84:52-59.

    Not in our library10.1016/j.ajhg.2008.11.010

  12. 12.
    Telomere Lengths, Pulmonary Fibrosis and Telomerase (TERT) Mutations · 2010
    No notice
  13. 13.

    Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, Loyd JE, Cosgrove GP, Lynch D, Groshong S, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet. 2013;45:613-620.

    Not in our library10.1038/ng.2609

  14. 14.

    Noth I, Zhang Y, Ma SF, Flores C, Barber M, Huang Y, Broderick SM, Wade MS, Hysi P, Scuirba J, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med. 2013;1:309-317.

    Not in our library10.1016/s2213-2600(13)70045-6

  15. 15.
    MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis · 2008
    No notice
  16. 16.

    Yu G, Kovkarova-Naumovski E, Jara P, Parwani A, Kass D, Ruiz V, Lopez-Otin C, Rosas IO, Gibson KF, Cabrera S, et al. Matrix metalloproteinase-19 is a key regulator of lung fibrosis in mice and humans. Am J Respir Crit Care Med. 2012;186:752-762.

    Not in our library10.1164/rccm.201202-0302oc

  17. 17.

    Deng Y, Li Z, Liu J, Wang Z, Cao Y, Mou Y, Fu B, Mo B, Wei J, Cheng Z, et al. Targeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis. Hum Mutat. 2018;39:1238–1245.

    Not in our library10.1002/humu.23566

  18. 18.

    Saha S, Shalova IN, Biswas SK. Metabolic regulation of macrophage phenotype and function. Immunol Rev. 2017;280:102-111.

    Not in our library10.1111/imr.12603

  19. 19.

    Ginhoux F, Guilliams M, Naik SH. Editorial: dendritic cell and macrophage nomenclature and classification. Front Immunol. 2016;7:168.

    Not in our library10.3389/fimmu.2016.00168

  20. 20.

    Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012;122:787-795.

    Not in our library10.1172/jci59643

  21. 21.

    Arora S, Dev K, Agarwal B, Das P, Syed MA. Macrophages: their role, activation and polarization in pulmonary diseases. Immunobiology. 2018;223:383-396.

    Not in our library10.1016/j.imbio.2017.11.001

  22. 22.

    Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11:889-896.

    Not in our library10.1038/ni.1937

  23. 23.

    Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M. Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol. 2013;229:176-185.

    Not in our library10.1002/path.4133

  24. 24.

    Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41:14-20.

    Not in our library10.1016/j.immuni.2014.06.008

  25. 25.

    Murray PJ. Macrophage polarization. Annu Rev Physiol. 2017;79:541-566.

    Not in our library10.1146/annurev-physiol-022516-034339

  26. 26.

    Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, Leboeuf M, Becker CD, See P, Price J, Lucas D, et al. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. 2013;38:792-804.

    Not in our library10.1016/j.immuni.2013.04.004

  27. 27.

    Epelman S, Lavine KJ, Randolph GJ. Origin and functions of tissue macrophages. Immunity. 2014;41:21-35.

    Not in our library10.1016/j.immuni.2014.06.013

  28. 28.

    Gordon S. Elie Metchnikoff: father of natural immunity. Eur J Immunol. 2008;38:3257-3264.

    Not in our library10.1002/eji.200838855

  29. 29.

    Divangahi M, King IL, Pernet E. Alveolar macrophages and type I IFN in airway homeostasis and immunity. Trends Immunol. 2015;36:307-314.

    Not in our library10.1016/j.it.2015.03.005

  30. 30.

    Stefater JA, Ren S, Lang RA, Duffield JS. Metchnikoff's policemen: macrophages in development, homeostasis and regeneration. Trends Mol Med. 2011;17:743-752.

    Not in our library10.1016/j.molmed.2011.07.009

  31. 31.

    van Furth R, Cohn ZA, Hirsch JG, Humphrey JH, Spector WG, Langevoort HL. The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bull World Health Organ. 1972;46:845-852.

    Not in our library

  32. 32.

    Marchesi VT, Florey HW. Electron micrographic observations on the emigration of leucocytes. Q J Exp Physiol Cogn Med Sci. 1960;45:343-348.

    Not in our library10.1113/expphysiol.1960.sp001489

  33. 33.

    Volkman A, Gowans JL. The origin of macrophages from bone marrow in the rat. Br J Exp Pathol. 1965;46:62-70.

    Not in our library

  34. 34.

    Yona S, Kim KW, Wolf Y, Mildner A, Varol D, Breker M, Strauss-Ayali D, Viukov S, Guilliams M, Misharin A, et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity. 2013;38:79-91.

    Not in our library10.1016/j.immuni.2012.12.001

  35. 35.

    Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496:445-455.

    Not in our library10.1038/nature12034

  36. 36.

    Guilliams M, De Kleer I, Henri S, Post S, Vanhoutte L, De Prijck S, Deswarte K, Malissen B, Hammad H, Lambrecht BN. Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J Exp Med. 2013;210:1977-1992.

    Not in our library10.1084/jem.20131199

  37. 37.

    Bedoret D, Wallemacq H, Marichal T, Desmet C, Quesada Calvo F, Henry E, Closset R, Dewals B, Thielen C, Gustin P, et al. Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice. J Clin Invest. 2009;119:3723-3738.

    Not in our library10.1172/jci39717

  38. 38.

    Desch AN, Gibbings SL, Goyal R, Kolde R, Bednarek J, Bruno T, Slansky JE, Jacobelli J, Mason R, Ito Y, et al. Flow cytometric analysis of mononuclear phagocytes in nondiseased human lung and lung-draining lymph nodes. Am J Respir Crit Care Med. 2016;193:614-626.

    Not in our library10.1164/rccm.201507-1376oc

  39. 39.

    Byrne AJ, Maher TM, Lloyd CM. Pulmonary macrophages: a new therapeutic pathway in Fibrosing lung disease? Trends Mol Med. 2016;22:303-316.

    Not in our library10.1016/j.molmed.2016.02.004

  40. 40.

    Van den Bossche J, Malissen B, Mantovani A, De Baetselier P, Van Ginderachter JA. Regulation and function of the E-cadherin/catenin complex in cells of the monocyte-macrophage lineage and DCs. Blood. 2012;119:1623-1633.

    Not in our library10.1182/blood-2011-10-384289

  41. 41.

    Misharin AV, Morales-Nebreda L, Reyfman PA, Cuda CM, Walter JM, McQuattie-Pimentel AC, Chen CI, Anekalla KR, Joshi N, Williams KJN, et al. Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. J Exp Med. 2017;214:2387-2404.

    Not in our library10.1084/jem.20162152

  42. 42.

    Scott CL, Henri S, Guilliams M. Mononuclear phagocytes of the intestine, the skin, and the lung. Immunol Rev. 2014;262:9-24.

    Not in our library10.1111/imr.12220

  43. 43.

    Cai Y, Sugimoto C, Arainga M, Alvarez X, Didier ES, Kuroda MJ. In vivo characterization of alveolar and interstitial lung macrophages in rhesus macaques: implications for understanding lung disease in humans. J Immunol. 2014;192:2821-2829.

    Not in our library10.4049/jimmunol.1302269

  44. 44.

    Ji WJ, Ma YQ, Zhou X, Zhang YD, Lu RY, Sun HY, Guo ZZ, Zhang Z, Li YM, Wei LQ. Temporal and spatial characterization of mononuclear phagocytes in circulating, lung alveolar and interstitial compartments in a mouse model of bleomycin-induced pulmonary injury. J Immunol Methods. 2014;403:7-16.

    Not in our library10.1016/j.jim.2013.11.012

  45. 45.

    Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25:677-686.

    Not in our library10.1016/j.it.2004.09.015

  46. 46.

    Locati M, Mantovani A, Sica A. Macrophage activation and polarization as an adaptive component of innate immunity. Adv Immunol. 2013;120:163-184.

    Not in our library10.1016/b978-0-12-417028-5.00006-5

  47. 47.

    Saradna A, Do DC, Kumar S, Fu QL, Gao P. Macrophage polarization and allergic asthma. Transl Res. 2018;191:1-14.

    Not in our library10.1016/j.trsl.2017.09.002

  48. 48.

    Murray PJ, Wynn TA. Obstacles and opportunities for understanding macrophage polarization. J Leukoc Biol. 2011;89:557-563.

    Not in our library10.1189/jlb.0710409

  49. 49.
    Molecular Mechanisms That Influence the Macrophage M1–M2 Polarization Balance · 2014
    No notice
  50. 50.

    Sierra-Filardi E, Vega MA, Sanchez-Mateos P, Corbi AL, Puig-Kroger A. Heme Oxygenase-1 expression in M-CSF-polarized M2 macrophages contributes to LPS-induced IL-10 release. Immunobiology. 2010;215:788-795.

    Not in our library10.1016/j.imbio.2010.05.020

  51. 51.

    van Tits LJ, Stienstra R, van Lent PL, Netea MG, Joosten LA, Stalenhoef AF. Oxidized LDL enhances pro-inflammatory responses of alternatively activated M2 macrophages: a crucial role for Kruppel-like factor 2. Atherosclerosis. 2011;214:345-349.

    Not in our library10.1016/j.atherosclerosis.2010.11.018

  52. 52.

    Tian S, Zhang L, Tang J, Guo X, Dong K, Chen SY. HMGB1 exacerbates renal tubulointerstitial fibrosis through facilitating M1 macrophage phenotype at the early stage of obstructive injury. Am J Physiol Renal Physiol. 2015;308:F69-F75.

    Not in our library10.1152/ajprenal.00484.2014

  53. 53.

    Shivshankar P, Halade GV, Calhoun C, Escobar GP, Mehr AJ, Jimenez F, Martinez C, Bhatnagar H, Mjaatvedt CH, Lindsey ML, Le Saux CJ. Caveolin-1 deletion exacerbates cardiac interstitial fibrosis by promoting M2 macrophage activation in mice after myocardial infarction. J Mol Cell Cardiol. 2014;76:84-93.

    Not in our library10.1016/j.yjmcc.2014.07.020

  54. 54.

    Nomura M, Liu J, Rovira II, Gonzalez-Hurtado E, Lee J, Wolfgang MJ, Finkel T. Fatty acid oxidation in macrophage polarization. Nat Immunol. 2016;17:216-217.

    Not in our library10.1038/ni.3366

  55. 55.

    Tarique AA, Logan J, Thomas E, Holt PG, Sly PD, Fantino E. Phenotypic, functional, and plasticity features of classical and alternatively activated human macrophages. Am J Respir Cell Mol Biol. 2015;53:676-688.

    Not in our library10.1165/rcmb.2015-0012oc

  56. 56.

    Burgy O, Konigshoff M. The WNT signaling pathways in wound healing and fibrosis. Matrix Biol. 2018;68-69:67-80.

    Not in our library10.1016/j.matbio.2018.03.017

  57. 57.

    Richards CD. Innate immune cytokines, fibroblast phenotypes, and regulation of extracellular matrix in lung. J Interf Cytokine Res. 2017;37:52-61.

    Not in our library10.1089/jir.2016.0112

  58. 58.

    Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity. 2016;44:450-462.

    Not in our library10.1016/j.immuni.2016.02.015

  59. 59.

    Weiss M, Byrne AJ, Blazek K, Saliba DG, Pease JE, Perocheau D, Feldmann M, Udalova IA. IRF5 controls both acute and chronic inflammation. Proc Natl Acad Sci U S A. 2015;112:11001-11006.

    Not in our library10.1073/pnas.1506254112

  60. 60.

    Xiang GA, Zhang YD, Su CC, Ma YQ, Li YM, Zhou X, Wei LQ, Ji WJ. Dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in a mouse model of experimental silicosis. Inhal Toxicol. 2016;28:393-402.

    Not in our library10.1080/08958378.2016.1188186

  61. 61.

    Gibbons MA, MacKinnon AC, Ramachandran P, Dhaliwal K, Duffin R, Phythian-Adams AT, van Rooijen N, Haslett C, Howie SE, Simpson AJ, et al. Ly6Chi monocytes direct alternatively activated profibrotic macrophage regulation of lung fibrosis. Am J Respir Crit Care Med. 2011;184:569-581.

    Not in our library10.1164/rccm.201010-1719oc

  62. 62.

    Osterholzer JJ, Olszewski MA, Murdock BJ, Chen GH, Erb-Downward JR, Subbotina N, Browning K, Lin Y, Morey RE, Dayrit JK, et al. Implicating exudate macrophages and Ly-6C(high) monocytes in CCR2-dependent lung fibrosis following gene-targeted alveolar injury. J Immunol. 2013;190:3447-3457.

    Not in our library10.4049/jimmunol.1200604

  63. 63.

    Sica A, Erreni M, Allavena P, Porta C. Macrophage polarization in pathology. Cell Mol Life Sci. 2015;72:4111-4126.

    Not in our library10.1007/s00018-015-1995-y

  64. 64.

    Mills CD, Ley K. M1 and M2 macrophages: the chicken and the egg of immunity. J Innate Immun. 2014;6:716-726.

    Not in our library10.1159/000364945

  65. 65.

    Toshchakov V, Jones BW, Lentschat A, Silva A, Perera PY, Thomas K, Cody MJ, Zhang S, Williams BR, Major J, et al. TLR2 and TLR4 agonists stimulate unique repertoires of host resistance genes in murine macrophages: interferon-beta-dependent signaling in TLR4-mediated responses. J Endotoxin Res. 2003;9:169-175.

    Not in our library10.1177/09680519030090030501

  66. 66.

    Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y, Prestwich GD, Mascarenhas MM, Garg HG, Quinn DA, et al. Regulation of lung injury and repair by toll-like receptors and hyaluronan. Nat Med. 2005;11:1173-1179.

    Not in our library10.1038/nm1315

  67. 67.

    Paun A, Fox J, Balloy V, Chignard M, Qureshi ST, Haston CK. Combined Tlr2 and Tlr4 deficiency increases radiation-induced pulmonary fibrosis in mice. Int J Radiat Oncol Biol Phys. 2010;77:1198-1205.

    Not in our library10.1016/j.ijrobp.2009.12.065

  68. 68.

    Ballinger MN, Newstead MW, Zeng X, Bhan U, Mo XM, Kunkel SL, Moore BB, Flavell R, Christman JW, Standiford TJ. IRAK-M promotes alternative macrophage activation and fibroproliferation in bleomycin-induced lung injury. J Immunol. 2015;194:1894-1904.

    Not in our library10.4049/jimmunol.1402377

  69. 69.

    Zhang H, Han G, Liu H, Chen J, Ji X, Zhou F, Zhou Y, Xie C. The development of classically and alternatively activated macrophages has different effects on the varied stages of radiation-induced pulmonary injury in mice. J Radiat Res. 2011;52:717-726.

    Not in our library10.1269/jrr.11054

  70. 70.

    He Z, Zhang H, Yang C, Zhou Y, Zhou Y, Han G, Xia L, Ouyang W, Zhou F, Zhou Y, Xie C. The interaction between different types of activated RAW 264.7 cells and macrophage inflammatory protein-1 alpha. Radiat Oncol. 2011;6:86.

    Not in our library10.1186/1748-717x-6-86

  71. 71.

    Samara KD, Antoniou KM, Karagiannis K, Margaritopoulos G, Lasithiotaki I, Koutala E, Siafakas NM. Expression profiles of toll-like receptors in non-small cell lung cancer and idiopathic pulmonary fibrosis. Int J Oncol. 2012;40:1397-1404.

    Not in our library10.3892/ijo.2012.1374

  72. 72.

    Liu HZ, Yang HZ, Mi S, Cui B, Hua F, Hu ZW. Toll like receptor 2 mediates bleomycin-induced acute lung injury, inflammation and fibrosis in mice. Yao Xue Xue Bao. 2010;45:976-986.

    Not in our library

  73. 73.

    Dalmas E, Toubal A, Alzaid F, Blazek K, Eames HL, Lebozec K, Pini M, Hainault I, Montastier E, Denis RG, et al. Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nat Med. 2015;21:610-618.

    Not in our library10.1038/nm.3829

  74. 74.

    Zhong B, Yang X, Sun Q, Liu L, Lan X, Tian J, He Q, Hou W, Liu H, Jiang C, et al. Pdcd4 modulates markers of macrophage alternative activation and airway remodeling in antigen-induced pulmonary inflammation. J Leukoc Biol. 2014;96:1065-1075.

    Not in our library10.1189/jlb.3a0313-136rrr

  75. 75.

    Wang Q, Ni H, Lan L, Wei X, Xiang R, Wang Y. Fra-1 protooncogene regulates IL-6 expression in macrophages and promotes the generation of M2d macrophages. Cell Res. 2010;20:701-712.

    Not in our library10.1038/cr.2010.52

  76. 76.

    Raes G, De Baetselier P, Noel W, Beschin A, Brombacher F, Hassanzadeh Gh G. Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages. J Leukoc Biol. 2002;71:597-602.

    Not in our library

  77. 77.
    FIZZ1 and Ym as Tools to Discriminate between Differentially Activated Macrophages · 2002
    No notice
  78. 78.

    Hong JY, Chung Y, Steenrod J, Chen Q, Lei J, Comstock AT, Goldsmith AM, Bentley JK, Sajjan US, Hershenson MB. Macrophage activation state determines the response to rhinovirus infection in a mouse model of allergic asthma. Respir Res. 2014;15:63.

    Not in our library10.1186/1465-9921-15-63

  79. 79.

    Zhu L, Yang T, Li L, Sun L, Hou Y, Hu X, Zhang L, Tian H, Zhao Q, Peng J, et al. TSC1 controls macrophage polarization to prevent inflammatory disease. Nat Commun. 2014;5:4696.

    Not in our library10.1038/ncomms5696

  80. 80.

    Yoshida K, Maekawa T, Zhu Y, Renard-Guillet C, Chatton B, Inoue K, Uchiyama T, Ishibashi K, Yamada T, Ohno N, et al. The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory. Nat Immunol. 2015;16:1034-1043.

    Not in our library10.1038/ni.3257

  81. 81.

    Wei Q, Sha Y, Bhattacharya A, Abdel Fattah E, Bonilla D, Jyothula SS, Pandit L, Khurana Hershey GK, Eissa NT. Regulation of IL-4 receptor signaling by STUB1 in lung inflammation. Am J Respir Crit Care Med. 2014;189:16-29.

    Not in our library10.1164/rccm.201305-0874oc

  82. 82.

    Zhang Q, Zhao K, Shen Q, Han Y, Gu Y, Li X, Zhao D, Liu Y, Wang C, Zhang X, et al. Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature. 2015;525:389-393.

    Not in our library10.1038/nature15252

  83. 83.

    Karo-Atar D, Itan M, Pasmanik-Chor M, Munitz A. MicroRNA profiling reveals opposing expression patterns for miR-511 in alternatively and classically activated macrophages. J Asthma. 2015;52:545-553.

    Not in our library10.3109/02770903.2014.988222

  84. 84.

    Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, Miyake T, Matsushita K, Okazaki T, Saitoh T, et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol. 2010;11:936-944.

    Not in our library10.1038/ni.1920

  85. 85.

    Chang HY, Lee HN, Kim W, Surh YJ. Docosahexaenoic acid induces M2 macrophage polarization through peroxisome proliferator-activated receptor gamma activation. Life Sci. 2015;120:39-47.

    Not in our library10.1016/j.lfs.2014.10.014

  86. 86.

    Liao X, Sharma N, Kapadia F, Zhou G, Lu Y, Hong H, Paruchuri K, Mahabeleshwar GH, Dalmas E, Venteclef N, et al. Kruppel-like factor 4 regulates macrophage polarization. J Clin Invest. 2011;121:2736-2749.

    Not in our library10.1172/jci45444

  87. 87.

    Yao Y, Wang Y, Zhang Z, He L, Zhu J, Zhang M, He X, Cheng Z, Ao Q, Cao Y, et al. Chop deficiency protects mice against bleomycin-induced pulmonary fibrosis by attenuating M2 macrophage production. Mol Ther. 2016;24:915-925.

    Not in our library10.1038/mt.2016.36

  88. 88.

    Van Dyken SJ, Locksley RM. Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu Rev Immunol. 2013;31:317-343.

    Not in our library10.1146/annurev-immunol-032712-095906

  89. 89.

    Duffield JS, Lupher M, Thannickal VJ, Wynn TA. Host responses in tissue repair and fibrosis. Annu Rev Pathol. 2013;8:241-276.

    Not in our library10.1146/annurev-pathol-020712-163930

  90. 90.

    Prasse A, Pechkovsky DV, Toews GB, Jungraithmayr W, Kollert F, Goldmann T, Vollmer E, Muller-Quernheim J, Zissel G. A vicious circle of alveolar macrophages and fibroblasts perpetuates pulmonary fibrosis via CCL18. Am J Respir Crit Care Med. 2006;173:781-792.

    Not in our library10.1164/rccm.200509-1518oc

  91. 91.

    Joshi AD, Raymond T, Coelho AL, Kunkel SL, Hogaboam CM. A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone-marrow-derived macrophages to toll-like receptor agonists. J Leukoc Biol. 2008;83:314-324.

    Not in our library10.1189/jlb.1007689

  92. 92.

    Liu T, Jin H, Ullenbruch M, Hu B, Hashimoto N, Moore B, McKenzie A, Lukacs NW, Phan SH. Regulation of found in inflammatory zone 1 expression in bleomycin-induced lung fibrosis: role of IL-4/IL-13 and mediation via STAT-6. J Immunol. 2004;173:3425-3431.

    Not in our library10.4049/jimmunol.173.5.3425

  93. 93.

    Sandler NG, Mentink-Kane MM, Cheever AW, Wynn TA. Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. J Immunol. 2003;171:3655-3667.

    Not in our library10.4049/jimmunol.171.7.3655

  94. 94.

    Sun L, Louie MC, Vannella KM, Wilke CA, LeVine AM, Moore BB, Shanley TP. New concepts of IL-10-induced lung fibrosis: fibrocyte recruitment and M2 activation in a CCL2/CCR2 axis. Am J Physiol Lung Cell Mol Physiol. 2011;300:L341-L353.

    Not in our library10.1152/ajplung.00122.2010

  95. 95.

    Song E, Ouyang N, Horbelt M, Antus B, Wang M, Exton MS. Influence of alternatively and classically activated macrophages on fibrogenic activities of human fibroblasts. Cell Immunol. 2000;204:19-28.

    Not in our library10.1006/cimm.2000.1687

  96. 96.

    Tiemessen MM, Jagger AL, Evans HG, van Herwijnen MJ, John S, Taams LS. CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc Natl Acad Sci U S A. 2007;104:19446-19451.

    Not in our library10.1073/pnas.0706832104

  97. 97.

    Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science. 2011;332:243-247.

    Not in our library10.1126/science.1201475

  98. 98.

    Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, Chawla A, Locksley RM. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med. 2013;210:535-549.

    Not in our library10.1084/jem.20121964

  99. 99.

    Morrison TJ, Jackson MV, Cunningham EK, Kissenpfennig A, McAuley DF, O'Kane CM, Krasnodembskaya AD. Mesenchymal stromal cells modulate macrophages in clinically relevant lung injury models by extracellular vesicle mitochondrial transfer. Am J Respir Crit Care Med. 2017;196:1275-1286.

    Not in our library10.1164/rccm.201701-0170oc

  100. 100.

    Liu G, Ma H, Qiu L, Li L, Cao Y, Ma J, Zhao Y. Phenotypic and functional switch of macrophages induced by regulatory CD4+CD25+ T cells in mice. Immunol Cell Biol. 2011;89:130-142.

    Not in our library10.1038/icb.2010.70

  101. 101.

    Liu X, Jiang S, Zhang Q, Xu S, Bao X, Cao W, Bai J, Tang L. Tim-3 regulates Tregs’ ability to resolve the inflammation and proliferation of acute lung injury by modulating macrophages polarization. Shock. 2017.

    Not in our library10.1097/shk.0000000000001070

  102. 102.

    Van Kaer L, Parekh VV, Wu L. Invariant natural killer T cells: bridging innate and adaptive immunity. Cell Tissue Res. 2011;343:43-55.

    Not in our library10.1007/s00441-010-1023-3

  103. 103.

    Grabarz F, Aguiar CF, Correa-Costa M, Braga TT, Hyane MI, Andrade-Oliveira V, Landgraf MA, Camara NOS. Protective role of NKT cells and macrophage M2-driven phenotype in bleomycin-induced pulmonary fibrosis. Inflammopharmacology. 2018;26:491-504.

    Not in our library10.1007/s10787-017-0383-7

  104. 104.

    Wills-Karp M, Finkelman FD. Untangling the complex web of IL-4- and IL-13-mediated signaling pathways. Sci Signal. 2008;1:pe55.

    Not in our library10.1126/scisignal.1.51.pe55

  105. 105.

    Guo X, Li T, Xu Y, Xu X, Zhu Z, Zhang Y, Xu J, Xu K, Cheng H, Zhang X, Ke Y. Increased levels of Gab1 and Gab2 adaptor proteins skew interleukin-4 (IL-4) signaling toward M2 macrophage-driven pulmonary fibrosis in mice. J Biol Chem. 2017;292:14003-14015.

    Not in our library10.1074/jbc.m117.802066

  106. 106.

    Kral JB, Kuttke M, Schrottmaier WC, Birnecker B, Warszawska J, Wernig C, Paar H, Salzmann M, Sahin E, Brunner JS, et al. Sustained PI3K activation exacerbates BLM-induced lung fibrosis via activation of pro-inflammatory and pro-fibrotic pathways. Sci Rep. 2016;6:23034.

    Not in our library10.1038/srep23034

  107. 107.

    Tao B, Jin W, Xu J, Liang Z, Yao J, Zhang Y, Wang K, Cheng H, Zhang X, Ke Y. Myeloid-specific disruption of tyrosine phosphatase Shp2 promotes alternative activation of macrophages and predisposes mice to pulmonary fibrosis. J Immunol. 2014;193:2801-2811.

    Not in our library10.4049/jimmunol.1303463

  108. 108.

    Karmouty-Quintana H, Philip K, Acero LF, Chen NY, Weng T, Molina JG, Luo F, Davies J, Le NB, Bunge I, et al. Deletion of ADORA2B from myeloid cells dampens lung fibrosis and pulmonary hypertension. FASEB J. 2015;29:50-60.

    Not in our library10.1096/fj.14-260182

  109. 109.

    Philip K, Mills TW, Davies J, Chen NY, Karmouty-Quintana H, Luo F, Molina JG, Amione-Guerra J, Sinha N, Guha A, et al. HIF1A up-regulates the ADORA2B receptor on alternatively activated macrophages and contributes to pulmonary fibrosis. FASEB J. 2017;31:4745-4758.

    Not in our library10.1096/fj.201700219r

  110. 110.

    Larson-Casey JL, Deshane JS, Ryan AJ, Thannickal VJ, Carter AB. Macrophage Akt1 kinase-mediated Mitophagy modulates apoptosis resistance and pulmonary fibrosis. Immunity. 2016;44:582-596.

    Not in our library10.1016/j.immuni.2016.01.001

  111. 111.

    Osborn-Heaford HL, Murthy S, Gu L, Larson-Casey JL, Ryan AJ, Shi L, Glogauer M, Neighbors JD, Hohl R, Carter AB. Targeting the isoprenoid pathway to abrogate progression of pulmonary fibrosis. Free Radic Biol Med. 2015;86:47-56.

    Not in our library10.1016/j.freeradbiomed.2015.04.031

  112. 112.

    Osborn-Heaford HL, Ryan AJ, Murthy S, Racila AM, He C, Sieren JC, Spitz DR, Carter AB. Mitochondrial Rac1 GTPase import and electron transfer from cytochrome c are required for pulmonary fibrosis. J Biol Chem. 2012;287:3301-3312.

    Not in our library10.1074/jbc.m111.308387

  113. 113.

    Kirichok Y, Krapivinsky G, Clapham DE. The mitochondrial calcium uniporter is a highly selective ion channel. Nature. 2004;427:360-364.

    Not in our library10.1038/nature02246

  114. 114.

    Patron M, Raffaello A, Granatiero V, Tosatto A, Merli G, De Stefani D, Wright L, Pallafacchina G, Terrin A, Mammucari C, Rizzuto R. The mitochondrial calcium uniporter (MCU): molecular identity and physiological roles. J Biol Chem. 2013;288:10750-10758.

    Not in our library10.1074/jbc.r112.420752

  115. 115.

    Gu L, Larson-Casey JL, Carter AB. Macrophages utilize the mitochondrial calcium uniporter for profibrotic polarization. FASEB J. 2017;31:3072-3083.

    Not in our library10.1096/fj.201601371r

  116. 116.

    He C, Ryan AJ, Murthy S, Carter AB. Accelerated development of pulmonary fibrosis via Cu,Zn-superoxide dismutase-induced alternative activation of macrophages. J Biol Chem. 2013;288:20745-20757.

    Not in our library10.1074/jbc.m112.410720

  117. 117.

    He C, Larson-Casey JL, Gu L, Ryan AJ, Murthy S, Carter AB. Cu,Zn-Superoxide Dismutase-Mediated Redox Regulation of Jumonji Domain Containing 3 Modulates Macrophage Polarization and Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2016;55:58-71.

    Not in our library10.1165/rcmb.2015-0183oc

  118. 118.

    Oh J, Riek AE, Weng S, Petty M, Kim D, Colonna M, Cella M, Bernal-Mizrachi C. Endoplasmic reticulum stress controls M2 macrophage differentiation and foam cell formation. J Biol Chem. 2012;287:11629-11641.

    Not in our library10.1074/jbc.m111.338673

  119. 119.

    Burman A, Tanjore H, Blackwell TS. Endoplasmic reticulum stress in pulmonary fibrosis. Matrix Biol. 2018;68-69:355-365.

    Not in our library10.1016/j.matbio.2018.03.015

  120. 120.

    Wang Y, Zhu J, Zhang L, Zhang Z, He L, Mou Y, Deng Y, Cao Y, Yang P, Su Y, et al. Role of C/EBP homologous protein and endoplasmic reticulum stress in asthma exacerbation by regulating the IL-4/signal transducer and activator of transcription 6/transcription factor EC/IL-4 receptor alpha positive feedback loop in M2 macrophages. J Allergy Clin Immunol. 2017;140:1550-1561.

    Not in our library10.1016/j.jaci.2017.01.024

  121. 121.

    Inomata M, Kamio K, Azuma A, Matsuda K, Kokuho N, Miura Y, Hayashi H, Nei T, Fujita K, Saito Y, Gemma A. Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis. Respir Res. 2014;15:16.

    Not in our library10.1186/1465-9921-15-16

  122. 122.

    Xiang J, Cheng S, Feng T, Wu Y, Xie W, Zhang M, Xu X, Zhang C. Neotuberostemonine attenuates bleomycin-induced pulmonary fibrosis by suppressing the recruitment and activation of macrophages. Int Immunopharmacol. 2016;36:158-164.

    Not in our library10.1016/j.intimp.2016.04.016

  123. 123.

    Ji WJ, Ma YQ, Zhou X, Zhang YD, Lu RY, Guo ZZ, Sun HY, Hu DC, Yang GH, Li YM, Wei LQ. Spironolactone attenuates bleomycin-induced pulmonary injury partially via modulating mononuclear phagocyte phenotype switching in circulating and alveolar compartments. PLoS One. 2013;8:e81090.

    Not in our library10.1371/journal.pone.0081090

  124. 124.

    Ji WJ, Ma YQ, Zhang X, Zhang L, Zhang YD, Su CC, Xiang GA, Zhang MP, Lin ZC, Wei LQ, et al. Inflammatory monocyte/macrophage modulation by liposome-entrapped spironolactone ameliorates acute lung injury in mice. Nanomedicine (Lond). 2016;11:1393-1406.

    Not in our library10.2217/nnm-2016-0006

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