Interleukin 33: an innate alarm for adaptive responses beyond Th2 immunity–emerging roles in obesity, intestinal inflammation, and cancer

Interleukin (IL)‐33, a member of the IL‐1 family, was originally described in 2005 as a potent initiator of type 2 immunity found during allergic inflammation and parasitic infections. IL‐33 has been shown to play important and potent roles bridging innate and adaptive immunity in the regulation of tissue homeostasis, injury, and repair. Recent discoveries have extended the range of functions for IL‐33 beyond type 2 conditions and its role as an alarmin at barrier sites, with emerging central roles for IL‐33 in T‐cell regulation, obesity, viral and tumor immunity. Here, we review the recent advances on how IL‐33 activity is regulated, its immunomodulatory properties on innate and adaptive cells, and the newly discovered roles of IL‐33 in obesity, intestinal inflammation, and tumorigenesis. This review highlights recent advances in IL‐33 biology beyond Th2 immunity: Novel mechanisms of regulation, its capacity to influence adaptive immune responses via innate cells, and emerging roles in obesity, intestinal inflammation, and tumorigenesis.