Interleukin (IL)-33: an orchestrator of immunity from host defence to tissue homeostasis

Interleukin (IL)-33, a member of the IL-1 superfamily, functions as an alarm signal, which is released upon cell injury or tissue damage to alert the immune system. It has emerged as a chief orchestrator in immunity and has a broad pleiotropic action that influences differentiation, maintenance and function of various immune cell types via the ST2 receptor. Although it has been strongly associated with immunopathology, critically, IL-33 is involved in host defence, tissue repair and homeostasis. In this review, we provide an overview of the signalling pathway of IL-33 and highlight its regulatory functions in immune cells. Furthermore, we attempt a broader discussion of the emerging functions of IL-33 in host defence, tissue repair, metabolism, inflammatory disease and cancer, suggesting potential avenues to manoeuvre IL-33/ST2 signalling as treatment options.