Elias Michael, Zhao Shuai, Le Hongnga T, Wang Jie, Neurath Markus F, Neufert Clemens, Fiocchi Claudio, Rieder Florian
Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.
J Clin Invest. 2021 Jan 19;131(2). doi: 10.1172/JCI144336.
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.
白细胞介素-36（IL-36）是白细胞介素-1超家族的成员，由三种激动剂和一种受体拮抗剂（IL-36Ra）组成。三种内源性激动剂，即IL-36α、-β和-γ，主要作为促炎细胞因子发挥作用，它们通过IL-36受体（IL-36R）发出的信号促进免疫细胞浸润以及炎症和趋化分子的分泌。然而，IL-36信号传导也促进促纤维化可溶性介质的分泌，提示其在纤维化疾病中发挥作用。IL-36同工型和IL-36已被证实与包括银屑病、关节炎、炎症性肠病和变应性鼻炎在内的炎症性疾病有关。此外，IL-36还与影响肾脏、肺和肠道的纤维化疾病相关。本综述总结了IL-36在各种器官的炎症和纤维化中的表达、细胞来源及功能，并提出调节IL-36可能对预防或治疗炎症性和纤维化疾病具有重要价值，且可能揭示炎症与纤维化之间的机制联系。
