Biological mechanisms and therapeutic prospects of interleukin-33 in pathogenesis and treatment of allergic disease

Allergic diseases significantly impact the quality of life of people around the world. Cytokines play a crucial role in regulating the immune system. Due to their importance in pro-inflammatory mechanisms, cytokines are used to understand pathogenesis and serve as biomarkers in many diseases. One such cytokine is interleukin-33, a member of the IL-1 family, including IL- 1α, IL-1β, and IL-18. The IL-33 receptor is a heterodimer of IL-1 receptor-like 1 and IL-1 receptor accessory protein. IL-33 plays a critical role in regulating innate and adaptive immune responses. The primary targets of IL-33 in vivo are tissue-resident immune cells, including mast cells, group 2 innate lymphoid cells, regulatory T cells, T helper 2 cells, eosinophils, basophils, dendritic cells, Th1 cells, CD8 + T cells, NK cells, iNKT cells, B cells, neutrophils, and macrophages. However, IL-33 appears to act as an alarm signal that is promptly released by producing cells under cellular damage or stress conditions. IL-33 regulates signaling and various biological functions, including induction of pro-inflammatory cytokines, regulation of cell proliferation, and involvement in tissue remodeling. IL-33 is fundamental in immune-related diseases and plays a critical role in the control of inflammation. Recently, IL-33 has been shown to significantly impact allergic diseases, primarily by inducing Th2 immune responses. IL-33 is a key regulator of mast cell function and a promising therapeutic target for treating allergic diseases. This review provides an overview of the current understanding of the role of IL-33 in allergy pathogenesis and potential clinical approaches.