Abstract: IL-33, a novel member of the IL-1 family, mediates its biological effects via the ST2 receptor (also known as IL-1RL1), and initiates a type 2 immune response during cardiovascular disease, Alzheimer′s disease, cancer and obesity. IL-33 is a dual-function protein that act both as a cytokine and as an intracellular nuclear factor. Here, we review the recent advances on how IL-33 activity is regulated by proteolysis and oxidation-driven conformational change of two disulphide bonds formation, and the newly discovered roles of IL-33 in atherosclerosis, obesity, rheumatoid arthritis, and Alzheimer′s disease. IL-33 mobilizes innate immunity and acquires immunity to initiate type-2 immune response by the IL-33/ST2L pathway. Therapeutic strategy targeting IL-33 may be an effective strategy to ameliorate these diseases.

Key words: IL-1 family, IL-33/ST2L signal, type 2 immune response, two disulphide bonds