IL-36 in chronic inflammation and fibrosis — bridging the gap?
Michael Elias,1,2 Shuai Zhao,1,2 Hongnga T. Le,1,2 Jie Wang,1,2,3 Markus F. Neurath,4 Clemens Neufert,4 Claudio Fiocchi,1,2 and Florian Rieder1,2
1Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
2Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.
3Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan Province, China.
4Department of Medicine 1 and Deutsches Zentrum Immuntherapie DZI, Universitaetsklinikum Erlangen, University of Erlangen-Nürnberg, Erlangen, Germany.
Address correspondence to: Florian Rieder, Department of Inflammation and Immunity, and Department of Gastroenterology, Hepatology & Nutrition, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. Phone: 216.445.4916; E-mail: riederf@ccf.org.
Authorship note: ME and SZ contributed equally to this work.
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1Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
2Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.
3Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan Province, China.
4Department of Medicine 1 and Deutsches Zentrum Immuntherapie DZI, Universitaetsklinikum Erlangen, University of Erlangen-Nürnberg, Erlangen, Germany.
Address correspondence to: Florian Rieder, Department of Inflammation and Immunity, and Department of Gastroenterology, Hepatology & Nutrition, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. Phone: 216.445.4916; E-mail: riederf@ccf.org.
Authorship note: ME and SZ contributed equally to this work.
Find articles by Zhao, S. in: JCI | PubMed | Google Scholar
1Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
2Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.
3Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan Province, China.
4Department of Medicine 1 and Deutsches Zentrum Immuntherapie DZI, Universitaetsklinikum Erlangen, University of Erlangen-Nürnberg, Erlangen, Germany.
Address correspondence to: Florian Rieder, Department of Inflammation and Immunity, and Department of Gastroenterology, Hepatology & Nutrition, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. Phone: 216.445.4916; E-mail: riederf@ccf.org.
Authorship note: ME and SZ contributed equally to this work.
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1Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
2Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.
3Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan Province, China.
4Department of Medicine 1 and Deutsches Zentrum Immuntherapie DZI, Universitaetsklinikum Erlangen, University of Erlangen-Nürnberg, Erlangen, Germany.
Address correspondence to: Florian Rieder, Department of Inflammation and Immunity, and Department of Gastroenterology, Hepatology & Nutrition, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. Phone: 216.445.4916; E-mail: riederf@ccf.org.
Authorship note: ME and SZ contributed equally to this work.
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1Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
2Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.
3Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan Province, China.
4Department of Medicine 1 and Deutsches Zentrum Immuntherapie DZI, Universitaetsklinikum Erlangen, University of Erlangen-Nürnberg, Erlangen, Germany.
Address correspondence to: Florian Rieder, Department of Inflammation and Immunity, and Department of Gastroenterology, Hepatology & Nutrition, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. Phone: 216.445.4916; E-mail: riederf@ccf.org.
Authorship note: ME and SZ contributed equally to this work.
Find articles by Neurath, M. in: JCI | PubMed | Google Scholar
1Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
2Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.
3Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan Province, China.
4Department of Medicine 1 and Deutsches Zentrum Immuntherapie DZI, Universitaetsklinikum Erlangen, University of Erlangen-Nürnberg, Erlangen, Germany.
Address correspondence to: Florian Rieder, Department of Inflammation and Immunity, and Department of Gastroenterology, Hepatology & Nutrition, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. Phone: 216.445.4916; E-mail: riederf@ccf.org.
Authorship note: ME and SZ contributed equally to this work.
Find articles by Neufert, C. in: JCI | PubMed | Google Scholar
1Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
2Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.
3Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan Province, China.
4Department of Medicine 1 and Deutsches Zentrum Immuntherapie DZI, Universitaetsklinikum Erlangen, University of Erlangen-Nürnberg, Erlangen, Germany.
Address correspondence to: Florian Rieder, Department of Inflammation and Immunity, and Department of Gastroenterology, Hepatology & Nutrition, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. Phone: 216.445.4916; E-mail: riederf@ccf.org.
Authorship note: ME and SZ contributed equally to this work.
Find articles by Fiocchi, C. in: JCI | PubMed | Google Scholar
1Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
2Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.
3Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan Province, China.
4Department of Medicine 1 and Deutsches Zentrum Immuntherapie DZI, Universitaetsklinikum Erlangen, University of Erlangen-Nürnberg, Erlangen, Germany.
Address correspondence to: Florian Rieder, Department of Inflammation and Immunity, and Department of Gastroenterology, Hepatology & Nutrition, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. Phone: 216.445.4916; E-mail: riederf@ccf.org.
Authorship note: ME and SZ contributed equally to this work.
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Rieder, F.
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Published January 19, 2021 - More info
J Clin Invest. 2021;131(2):e144336. https://doi.org/10.1172/JCI144336.
© 2021 American Society for Clinical Investigation
IL-36 is a member of the IL-1 superfamily and consists of three agonists and one receptor antagonist (IL-36Ra). The three endogenous agonists, IL-36α, –β, and –γ, act primarily as proinflammatory cytokines, and their signaling through the IL-36 receptor (IL-36R) promotes immune cell infiltration and secretion of inflammatory and chemotactic molecules. However, IL-36 signaling also fosters secretion of profibrotic soluble mediators, suggesting a role in fibrotic disorders. IL-36 isoforms and IL-36 have been implicated in inflammatory diseases including psoriasis, arthritis, inflammatory bowel diseases, and allergic rhinitis. Moreover, IL-36 has been connected to fibrotic disorders affecting the kidney, lung, and intestines. This review summarizes the expression, cellular source, and function of IL-36 in inflammation and fibrosis in various organs, and proposes that IL-36 modulation may prove valuable in preventing or treating inflammatory and fibrotic diseases and may reveal a mechanistic link between inflammation and fibrosis.
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