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


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.

SUBMITTER: Elias M 

PROVIDER: S-EPMC7810483 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Elias Michael M   Zhao Shuai S   Le Hongnga T HT   Wang Jie J   Neurath Markus F MF   Neufert Clemens C   Fiocchi Claudio C   Rieder Florian F  

The Journal of clinical investigation 20210101 2


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-3  ...[more]

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