The role of IL-37 in inflammatory bowel disease and colitis-associated colorectal cancer

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disorder of intestine and a high risk for colorectal cancer; however, its precise etiology and pathogenesis remain poorly understood. Interleukin (IL)-37, a member of IL-1 family, exerts anti-inflammatory effects in various inflammatory diseases and cancers, and is generated by several epithelial cells and immune cells. Mechanistically, IL-37 mediates its anti-inflammatory either by translocating into nucleus in complex with small mother against decapentaplegic homolog 3 or binding to extracellular interleukin-18 receptor and IL-1 receptor-related receptor 8 (IL-1R8), which is abundantly expressed in the gastrointestinal tract. Recently, accumulating evidence has demonstrated that IL-37 expression is upregulated and plays protective roles in IBD and colitis-associated cancer (CAC). This review summarizes the recent advances regarding the expression, biological functions, molecular mechanism, and therapeutic potential of IL-37 in IBD and CAC, aiming to provide novel insights into its underlying mechanism and clinical application.