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Role of anti-inflammatory cytokines IL-4 and IL-13 in systemic sclerosis

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Abstract

Objective

The aim of this paper is to review the anti-inflammatory cytokines IL-4 and IL-13 and their receptor signals; we discuss new insight into their possible roles in systemic sclerosis (SSc) and their overlapping function in SSc.

Introduction

SSc is a connective tissue disease characterized by fibrosis. The exact etiology of SSc is unknown, and no therapy has been proved effective in modifying its course. Recently the roles of IL-4 and IL-13 in the development of SSc have been extensively considered. The possible roles of IL-4 and IL-13, especially their overlapping function, in SSc are not well documented.

Methods

A literature survey was performed using a PubMed database search to gather complete information regarding IL-4 and IL-13 and their role in inflammation.

Results and conclusions

The participation of complex pathways of IL-4 and IL-13 in the process of inflammation and fibrosis action in SSc is still not very clear, and some pathogenesis of regulation found in vitro needs to be further proved. There is still more work which could be done to achieve useful developments with therapeutic benefit in SSc.

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References

  1. Naraghi K, van Laar JM. Update on stem cell transplantation for systemic sclerosis: recent trial results. Curr Rheumatol Rep. 2013;15(5):326.

    Article  PubMed  Google Scholar 

  2. Varga J, Abraham D. Systemic sclerosis: a prototype multisystem fibrotic disorder. J Clin Invest. 2007;117(3):557–67.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Barnes J, Mayes MD. Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers. Curr Opin Rheumatol. 2012;24(2):165–70.

    Article  PubMed  Google Scholar 

  4. Fett N. Scleroderma nomenclature, etiology, pathogenesis, prognosis, and treatments facts and controversies. Clin Dermatol. 2013;31(4):432–7.

    Article  PubMed  Google Scholar 

  5. Parel Y, Aurrand-Lions M, Scheja A, et al. Presence of CD4+CD8+double-positive T cells with very high interleukin-4 production potential in lesional skin of patients with systemic sclerosis. Arthritis Rheum. 2007;56(10):3459–67.

    Article  CAS  PubMed  Google Scholar 

  6. Muangchan C, Pope JE. Interleukin 6 in systemic sclerosis and potential implications for targeted therapy. J Rheumatol. 2012;39(6):1120–4.

    Article  CAS  PubMed  Google Scholar 

  7. Salim PH, Jobim M, Bredemeier M, et al. Interleukin-10 gene promoter and NFKB1 promoter insertion/deletion polymorphisms in systemic sclerosis. Scand J Immunol. 2013;77(2):162–8.

    Article  CAS  PubMed  Google Scholar 

  8. Fuschiotti P. Role of IL-13 in systemic sclerosis. Cytokine. 2011;56(3):544–9.

    Article  CAS  PubMed  Google Scholar 

  9. Truchetet ME, Brembilla NC, Montanari E, et al. Interleukin-17A+cells are increased in systemic sclerosis skin and their number is inversely correlated to the extent of skin involvement. Arthritis Rheum. 2013;. doi:10.1002/art.37860.

    PubMed  Google Scholar 

  10. Pehlivan Y, Onat AM, Ceylan N, et al. Serum leptin, resistin and TNF-α levels in patients with systemic sclerosis: the role of adipokines in scleroderma. Int J Rheum Dis. 2012;15(4):374–9.

    Article  CAS  PubMed  Google Scholar 

  11. Giordano N, Papakostas P, Pecetti G, et al. Cytokine modulation by endothelin-1 and possible therapeutic implications in systemic sclerosis. J Biol Regul Homeost Agents. 2011;25(4):487–92.

    CAS  PubMed  Google Scholar 

  12. Chomarat P, Banchereau J. Interleukin-4 and interleukin-13: their similarities and discrepancies. Int Rev Immunol. 1998;17(1–4):1–52.

    Article  CAS  PubMed  Google Scholar 

  13. Yao X, Zha W, Song W, et al. Coordinated regulation of IL-4 and IL-13 expression in human T cells: 3C analysis for DNA looping. Biochem Biophys Res Commun. 2012;417(3):996–1001.

    Article  CAS  PubMed  Google Scholar 

  14. Paul WE, Zhu J. How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol. 2010;10(4):225–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Liang HE, Reinhardt RL, Bando JK, et al. Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity. Nat Immunol. 2011;13(1):58–66.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Gallo E, Katzman S, Villarino AV. IL-13-producing Th1 and Th17 cells characterize adaptive responses to both self and foreign antigens. Eur J Immunol. 2012;42(9):2322–8.

    Article  CAS  PubMed  Google Scholar 

  17. Wills-Karp M, Finkelman FD. Untangling the complex web of IL-4- and IL-13-mediated signaling pathways. Sci Signal. 2008;1(51):pe55

  18. Tabata Y, Khurana Hershey GK. IL-13 receptor isoforms: breaking through the complexity. Curr Allergy Asthma Rep. 2007;7(5):338–45.

    Article  CAS  PubMed  Google Scholar 

  19. Wijesundara DK, Tscharke DC, Jackson RJ, et al. Reduced interleukin-4 receptor α expression on CD8 + T cells correlates with higher quality anti-viral immunity. PLoS One. 2013;8(1):e55788.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Lacy ER. Equilibrium and kinetic analysis of human interleukin-13 and IL-13 receptor alpha-2 complex formation. J Mol Recognit. 2012;25(3):184–91.

    Article  CAS  PubMed  Google Scholar 

  21. Ryan JJ, McReynolds LJ, Keegan A, et al. Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor. Immunity. 1996;4:123–32.

    Article  CAS  PubMed  Google Scholar 

  22. Hershey GK. IL-13 receptors and signaling pathways: an evolving web. Allergy Clin Immunol. 2003;4(111):677–90.

    Article  Google Scholar 

  23. Kelly-Welch AE, Hanson EM, Boothby MR, et al. Interleukin-4 and interleukin-13 signaling connections maps. Science. 2003;300(5625):1527–8.

    Article  CAS  PubMed  Google Scholar 

  24. Sun XJ, Wang LM, Zhang Y, et al. Role of IRS-2 in insulin and cytokine signaling. Nature. 1995;377:173–7.

    Article  CAS  PubMed  Google Scholar 

  25. White MF. The IRS-signaling system: a network of docking proteins that mediate insulin and cytokine action. Recent Prog Horm Res. 1998;53:119–38.

    CAS  PubMed  Google Scholar 

  26. Bhattacharjee A, Shukla M, Yakubenko VP, et al. IL-4 and IL-13 employ discrete signaling pathways for target gene expression in alternatively activated monocytes/macrophages. Free Radic Biol Med. 2013;54:1–16.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Junttila IS, Mizukami K, Dickensheets H, et al. Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4Rα, IL-13Rα1, and γc regulates relative cytokine sensitivity. J Exp Med. 2008;205(11):2595–608.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Andrews AL, Nordgren IK, Campbell-Harding G, et al. The association of the cytoplasmic domains of interleukin-4 receptor alpha and interleukin-13 receptor alpha 2 regulates interleukin-4 signaling. Mol BioSyst. 2013;9(12):3009–14.

    Article  CAS  PubMed  Google Scholar 

  29. Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol. 2004;4:583–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Kanellakis P, Ditiatkovski M, Kostolias G, Bobik A. A pro-fibrotic role for interleukin-4 in cardiac pressure overload. Cardiovasc Res. 2012;95(1):77–85.

    Article  CAS  PubMed  Google Scholar 

  31. Huaux F, Liu T, McGarry B, Ullenbruch M, Phan SH. Dual roles of IL-4 in lung injury and fibrosis. J Immunol. 2003;170(4):2083–92.

    Article  CAS  PubMed  Google Scholar 

  32. Saito A, Okazaki H, Sugawara I, Yamamoto K. Potential action of IL-4 and IL-13 as fibrogenic factors on lung fibroblasts in vitro. Int Arch Allergy Immunol. 2003;132(2):168–76.

    Article  CAS  PubMed  Google Scholar 

  33. Sugimoto R, Enjoji M, Nakamuta M, Ohta S. Effect of IL-4 and IL-13 on collagen production in cultured LI90 human hepatic stellate cells. Liver Int. 2005;25(2):420–8.

    Article  CAS  PubMed  Google Scholar 

  34. Sommer M, Eismann U, Gerth J, Stein G. Interleukin 4 co-stimulates the PDGF-BB and bFGF-mediated proliferation of mesangial cells and myofibroblasts. Nephron. 2002;92:868–80.

    Article  CAS  PubMed  Google Scholar 

  35. Sempowski GD, Beckmann MP, Derdak S, Phipps RP. Subsets of murine lung fibroblasts express membrane-bound and soluble IL-4 receptors. Role of IL-4 in enhancing fibroblast proliferation and collagen synthesis. J Immunol. 1994;152:3606–14.

    CAS  PubMed  Google Scholar 

  36. Postlethwaite AE, Holness MA, Katai H, Raghow R. Human fibroblasts synthesize elevated levels of extracellular matrix proteins in response to interleukin 4. J Clin Invest. 1992;90:1479–85.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Aoudjehane L, Pissaia A Jr, Scatton O, Podevin P, Massault PP, Chouzenoux S, et al. Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the stat-6 pathway. Lab Invest. 2008;88:973–85.

    Article  CAS  PubMed  Google Scholar 

  38. McGaha TL, Le M, Kodera T, Stoica C. Molecular mechanisms of interleukin-4-induced up-regulation of type I collagen gene expression in murine fibroblasts. Arthritis Rheum. 2003;48(8):2275–84.

    Article  CAS  PubMed  Google Scholar 

  39. Wynes MW, Riches DW. Induction of macrophage insulin-like growth factor-I expression by the Th2 cytokines IL-4 and IL-13. J Immunol. 2003;171(7):3550–9.

    Article  CAS  PubMed  Google Scholar 

  40. Wynes MW, Franke SK, Riches DW. IL-4-induced macrophage-derived IGF-I protects myofibroblasts from apoptosis following growth factor withdrawal. J Leukoc Biol. 2004;76(5):1019–27.

    Article  CAS  PubMed  Google Scholar 

  41. Jenkins SJ, Ruckerl D, Cook PC, Jones LH, Finkelman FD, van Rooijen N, et al. Local macrophage proliferation, rather than recruitment from the blood, is a signature of Th2 inflammation. Science. 2011;332:1284–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010;32:593–604.

    Article  CAS  PubMed  Google Scholar 

  43. Prokop S, Heppner FL, Goebel HH, Stenzel W. M2 polarized macrophages and giant cells contribute to myofibrosis in neuromuscular sarcoidosis. Am J Pathol. 2011;178:1279–86.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Bellini A, Marini MA, Bianchetti L, Barczyk M, Schmidt M, Mattoli S. Interleukin (IL)-4, IL-13, and IL-17A differentially affect the profibrotic and proinflammatory functions of fibrocytes from asthmatic patients. Mucosal Immunol. 2012;5(2):140–9.

    Article  CAS  PubMed  Google Scholar 

  45. Zhou Y, Hagood JS, Murphy-Ullrich JE. Thy-1 expression regulates the ability of rat lung fibroblasts to activate transforming growth factor-beta in response to fibrogenic stimuli. Am J Pathol. 2004;165:659–69.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Firszt R, Francisco D, Church TD, Thomas JM. Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma. Eur Respir J. 2014;43(2):464–73.

    Article  CAS  PubMed  Google Scholar 

  47. Sugimoto R, Enjoji M, Nakamuta M, Ohta S. Effect of IL-4 and IL-13 on collagen production in cultured LI90 human hepatic stellate cells. Liver Int. 2005;25(2):420–8.

    Article  CAS  PubMed  Google Scholar 

  48. Ingram JL, Rice A, Geisenhoffer K, Madtes DK. Interleukin-13 stimulates the proliferation of lung myofibroblasts via a signal transducer and activator of transcription-6-dependent mechanism: a possible mechanism for the development of airway fibrosis in asthma. Chest. 2003;123(3 Suppl):422S–4S.

    Article  CAS  PubMed  Google Scholar 

  49. Lu J, Zhu Y, Feng W, Pan Y. Platelet-derived growth factor mediates interleukin-13-induced collagen I production in mouse airway fibroblasts. J Biosci. 2014;39(4):693–700.

    Article  CAS  PubMed  Google Scholar 

  50. Lee CG, Homer RJ, Zhu Z, Lanone S. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta (1). J Exp Med. 2001;194(6):809–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Fichtner-Feigl S, Strober W, Kawakami K, Puri RK, Kitani A. IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Nat Med. 2006;12(1):99–106.

    Article  CAS  PubMed  Google Scholar 

  52. Kaviratne M, Hesse M, Leusink M, Cheever AW. IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independent. J Immunol. 2004;173(6):4020–9.

    Article  CAS  PubMed  Google Scholar 

  53. Hasegawa M, Fujimoto M, Kikuchi K, Takehara K. Elevated serum levels of interleukin 4 (IL-4), IL-10, and IL-13 in patients with systemic sclerosis. J Rheumatol. 1997;24(2):328–32.

    CAS  PubMed  Google Scholar 

  54. Salmon-Ehr V, Serpier H, Nawrocki B, Gillery P, Clavel C, Kalis B, Birembaut P, Maquart FX. Expression of interleukin-4 in scleroderma skin specimens and scleroderma fibroblast cultures. Potential role in fibrosis. Arch Dermatol. 1996;132(7):802–6.

    Article  CAS  PubMed  Google Scholar 

  55. Distler JH, Jüngel A, Caretto D, et al. Monocyte chemoattractant protein 1 released from glycosaminoglycans mediates its profibrotic effects in systemic sclerosis via the release of interleukin-4 from T cells. Arthritis Rheum. 2006;54(1):214–25.

    Article  CAS  PubMed  Google Scholar 

  56. Ong C, Wong C, Roberts CR, Teh HS, Jirik FR. Anti-IL-4 treatment prevents dermal collagen deposition in the tight-skin mouse model of scleroderma. Eur J Immunol. 1998;28(9):2619–29.

    Article  CAS  PubMed  Google Scholar 

  57. Binai N, O’Reilly S, Griffiths B, et al. Differentiation potential of CD4 + monocytes into myofibroblasts in patients with systemic sclerosis. PLoS One. 2012;7(3):e33508.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Lee KS, Ro YJ, Ryoo YW, Kwon HJ, Song JY. Regulation of interleukin-4 on collagen gene expression by systemic sclerosis fibroblasts in culture. J Dermatol Sci. 1996;12(2):110–7.

    Article  CAS  PubMed  Google Scholar 

  59. Greenblatt MB, Aliprantis AO. The immune pathogenesis of scleroderma: context is everything. Curr Rheumatol Rep. 2013;15(1):297.

    Article  PubMed Central  PubMed  Google Scholar 

  60. Riccieri V, Rinaldi T, Spadaro A, Scrivo R, Ceccarelli F, Franco MD, Taccari E, Valesini G. Interleukin-13 in systemic sclerosis: relationship to nailfold capillaroscopy abnormalities. Clin Rheumatol. 2003;22(2):102–6.

    Article  CAS  PubMed  Google Scholar 

  61. Hasegawa M, Sato S, Nagaoka T, Fujimoto M, Takehara K. Serum levels of tumor necrosis factor and interleukin-13 are elevated in patients with localized scleroderma. Dermatology. 2003;207(2):141–7.

    Article  CAS  PubMed  Google Scholar 

  62. Christmann RB, Hayes E, Pendergrass S, Padilla C, Farina G, Affandi AJ, Whitfield ML, Farber HW, Lafyatis R. Interferon and alternative activation of monocyte/macrophages in systemic sclerosis-associated pulmonary arterial hypertension. Arthritis Rheum. 2011;63(6):1718–28.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Fuschiotti P, Medsger TA, Morel PA. Effector CD8+T cells in systemic sclerosis patients produce abnormally high levels of interleukin-13 associated with increased skin fibrosis. Arthritis Rheum. 2009;60(4):1119–28.

    Article  CAS  PubMed  Google Scholar 

  64. Medsger TA Jr, Ivanco DE, Kardava L, et al. GATA-3 upregulation in CD8+T cells is a biomarker of immune dysfunction in systemic sclerosis, resulting in excess IL-13 production. Arthritis Rheum. 2011;63(6):1738–47.

    Article  PubMed  Google Scholar 

  65. Broen JC, Dieude P, Vonk MC, et al. Polymorphisms in the interleukin 4, interleukin 13, and corresponding receptor genes are not associated with systemic sclerosis and do not influence gene expression. J Rheumatol. 2012;39(1):112–8.

    Article  CAS  PubMed  Google Scholar 

  66. Granel B, Chevillard C, Allanore Y, et al. Evaluation of interleukin 13 polymorphisms in systemic sclerosis. Immunogenetics. 2006;58:693–9.

    Article  CAS  PubMed  Google Scholar 

  67. Granel B, Allanore Y, Chevillard C, et al. IL13RA2 gene polymorphisms are associated with systemic sclerosis. J Rheumatol. 2006;33:2015–9.

    CAS  PubMed  Google Scholar 

  68. O’Garra Anne, Arai Naoko. The molecular basis of T helper 1 and T helper 2 cell differentiation. Trends Cell Biol. 2000;10(12):542–50.

    Article  PubMed  Google Scholar 

  69. Lombardelli L, Aguerre-Girr M, Logiodice F, et al. HLA-G5 induces IL-4 secretion critical for successful pregnancy through differential expression of ILT2 receptor on decidual CD4+T cells and macrophages. J Immunol. 2013;191(7):3651–62.

    Article  CAS  PubMed  Google Scholar 

  70. Kuroda Etsushi, Antignano Frann, Ho Victor W, et al. SHIP represses Th2 skewing by inhibiting IL-4 production from basophils. J Immunol. 2011;186:323–32.

    Article  CAS  PubMed  Google Scholar 

  71. Cannons JL, Wu JZ, Gomez-Rodriguez J, et al. Biochemical and genetic evidence for a SAP-PKC-θ interaction contributing to IL-4 regulation. J Immunol. 2010;185:2819–27.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Bruhn S, Katzenellenbogen M, Gustafsson M, et al. Combining gene expression microarray- and cluster analysis with sequence-based predictions to identify regulators of IL-13 in allergy. Cytokine. 2012;60(3):736–40.

    Article  CAS  PubMed  Google Scholar 

  73. Kumar Manish, Ahmad Tanveer, Sharma Amit, et al. Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immun. 2011;128(5):1077–85.

    Article  CAS  PubMed  Google Scholar 

  74. Elo LL, Järvenpää H, Tuomela S, et al. Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming. Immunity. 2010;32(6):852–62.

    Article  CAS  PubMed  Google Scholar 

  75. Zhou M, Ouyang W. The function role of GATA-3 in Th1 and Th2 Differentiation. Immunol Res. 2003;28:25–37.

    Article  CAS  PubMed  Google Scholar 

  76. O’Reilly S, Hügle T, van Laar JM. T cells in systemic sclerosis: a reappraisal. Rheumatology. 2012;51:1540–9.

    Article  PubMed  Google Scholar 

  77. Divekar AA, Khanna D, Abtin F, Maranian P, Saggar R, Saggar R, Furst DE, Singh RR. Treatment with imatinib results in reduced IL-4-producing T cells, but increased CD4(+) T cells in the broncho-alveolar lavage of patients with systemic sclerosis. Clin Immunol. 2011;141(3):293–303.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Lightwood D, O’Dowd V, Carrington B, et al. The discovery, engineering and characterisation of a highly potent anti-human IL-13 fab fragment designed for administration by inhalation. J Mol Biol. 2013;425(3):577–93.

    Article  CAS  PubMed  Google Scholar 

  79. Greenblatt MB, Sargent JL, Farina G, et al. Interspecies comparison of human and murine scleroderma reveals IL-13 and CCL2 as disease subset-specific targets. Am J Pathol. 2012;180(3):1080–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Brown M, Postlethwaite AE, Myers LK, et al. Supernatants from culture of type I collagen-stimulated PBMC from patients with cutaneous systemic sclerosis versus localized scleroderma demonstrate suppression of MMP-1 by fibroblasts. Clin Rheumatol. 2012;31(6):973–81.

    Article  PubMed Central  PubMed  Google Scholar 

  81. Christmann RB, Mathes A, Affandi AJ, et al. TSLP upregulation in human SSc skin and induction of overlapping profibrotic genes and intracelullar signaling with IL-13 and TGFβ. Arthritis Rheum. 2013; doi: 10.1002

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Acknowledgments

This work was partly supported by grants from the Academic Leader Foundation of Anhui Medical University, the Natural Science Foundation of Anhui Province in 2013 (code 1308085MH169), and the Key Project of the Education Department of Anhui Province Natural Science Research (code KJ2012A165).

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, No. 81, Meishan Road, 230032, Hefei, Anhui, People’s Republic of China

    Xiao-Lei Huang, Yu-Jie Wang, Jun-Wei Yan, Ya-Nan Wan, Bao-Zhu Li & Jing Wang

  2. School of Basic Medicine, Anhui Medical University, Hefei, China

    Bing Chen

  3. Department of Rheumatology and Immunology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China

    Guo-Jun Yang

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  1. Xiao-Lei Huang
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Correspondence to Jing Wang.

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Responsible Editor: John Di Battista.

Authors X.-L. Huang and Y.-J. Wang contributed equally to this work and should be considered co-first authors.

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Huang, XL., Wang, YJ., Yan, JW. et al. Role of anti-inflammatory cytokines IL-4 and IL-13 in systemic sclerosis. Inflamm. Res. 64, 151–159 (2015). https://doi.org/10.1007/s00011-015-0806-0

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