IL-33 is a member of the IL-1 cytokine superfamily.It is a key regulator of pathological inflammation,immune ho-meostasis and fibrosis.IL-33 receptor ST2 is expressed on the surface of all innate immune cells,as well as some subtypes of B and T cells.IL-33 is a dual-function protein.Under normal circumstances,the N-terminal part of IL-33 resides in the nucleus of its ex-pressed cells and is released as a cytokine to exert immunomodulatory properties when cells are damaged or necrotic.Different expres-sion forms of IL-33 are located differently and may play different immunological roles.The immunological effects of IL-33 are highly di-verse.The cytokine IL-33 plays an amplifying and enhancing role in the innate immune response,while the full-length(FL)IL-33 stored in the nucleus inhibits inflammation by binding to NF-κB.IL-33/ST2 signaling plays a key role in both innate and acquired im-mune responses.In innate immunity,IL-33 and group 2 innate lymphocytes(ILC2)provide an important axis for rapid immune re-sponse and tissue homeostasis.In acquired immunity,IL-33 interacts with dendritic cells,Th2 cells,follicular helper T cells(Tfh)and regulatory T cells(Tregs).IL-33/ST2 signaling triggers pro-tumor or anti-tumor immune responses in different cell types in auto-crine and paracrine ways.In addition,the interaction between IL-33 and mitochondrial metabolism is also one of the potential mecha-nisms affecting the immune system.
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