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
  • 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.