2. Academic Validation
  3. IL-36 in chronic inflammation and fibrosis - bridging the gap?

IL-36 in chronic inflammation and fibrosis - bridging the gap?

  • J Clin Invest. 2021 Jan 19;131(2):e144336. doi: 10.1172/JCI144336.
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,  Florian Rieder 1 2
Affiliations

Affiliations

  • 1 Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
  • 2 Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.
  • 3 Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan Province, China.
  • 4 Department of Medicine 1 and Deutsches Zentrum Immuntherapie DZI, Universitaetsklinikum Erlangen, University of Erlangen-Nürnberg, Erlangen, Germany.
PMID: 33463541 DOI: 10.1172/JCI144336
Abstract

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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