Suppression of innate inflammation and immunity by interleukin‐37. Issue 5 (May 2016)

• Record Type: Journal Article
• Authors: Dinarello, Charles A.; Nold‐Petry, Claudia; Nold, Marcel; Fujita, Mayumi; Li, Suzhao; Kim, Soohyun; Bufler, Philip
• Is Part Of: European journal of immunology. Volume 46:Issue 5(2016)
• Page Start: 1067
• Page End: 1081
• Publication Date: 2016-05
• Subjects: Autoinflammation -- Caspase‐1 -- IL‐1 family -- Toll receptors; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201545828
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : Broad suppressive effects of IL‐37 affect both innate inflammation and the acquired immune response. The anti‐inflammatory properties of IL‐37 extend to the metabolic processes of the cell by reversing the Warburg effect, a fundamental characteristic of inflammation. The induction of tolerogenic dendritic cells accounts for the immunosuppression by IL‐37. Abstract : IL‐37 is unique in the IL‐1 family in that unlike other members of the family, IL‐37 broadly suppresses innate immunity. IL‐37 can be elevated in humans with inflammatory and autoimmune diseases where it likely functions to limit inflammation. Transgenic mice expressing human IL‐37 ( IL37 ‐tg) exhibit less severe inflammation in models of endotoxin shock, colitis, myocardial infarction, lung, and spinal cord injury. IL37 ‐tg mice have reduced antigen‐specific responses and dendritic cells (DCs) from these mice exhibit characteristics of tolerogenic DCs. Compared to aging wild‐type (WT) mice, aging IL37 ‐tg mice are protected against B‐cell leukemogenesis and heart failure. Treatment of WT mice with recombinant human IL‐37 has been shown to be protective in several models of inflammation and injury. IL‐37 binds to the IL‐18 receptor but then recruits the orphan IL‐1R8 (formerly TIR8 or SIGIRR) in order to function as an inhibitor. Here, we review the discovery of IL‐37, its production, release, and mechanisms by which IL‐37 reduces inflammation and suppresses immune responses. The data reviewed here suggest a therapeutic potential for IL‐37.