Suppression of innate inflammation and immunity by interleukin‐37

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.