Interleukin (IL)-33 and the IL-1 Family of Cytokines-Regulators of Inflammation and Tissue Homeostasis.

Cytokines play an integral role in shaping innate and adaptive immune responses. Members of the interleukin (IL)-1 family regulate a plethora of immune-cell-mediated processes, which include pathogen defense and tissue homeostasis. Notably, the IL-1 family cytokine IL-33 promotes adaptive and innate type 2 immune responses, confers viral protection and facilitates glucose metabolism and tissue repair. At the cellular level, IL-33 stimulates differentiation, maintenance, and function of various immune cell types, including regulatory T cells, effector CD4+ and CD8+ T cells, macrophages, and type 2 innate lymphoid cells (ILC2s). Other IL-1 family members, such as IL-1β and IL-18 promote type 1 responses, while IL-37 limits immune activation. Although IL-1 cytokines play critical roles in immunity and tissue repair, their deregulated expression is often linked to autoimmune and inflammatory diseases. Therefore, IL-1 cytokines are regulated tightly by posttranscriptional mechanisms and decoy receptors. In this review, we discuss the biology and function of IL-1 family cytokines, with a specific focus on regulation and function of IL-33 in immune and tissue homeostasis.