IL-33 induces both regulatory B cells and regulatory T cells in dextran sulfate sodium-induced colitis.

Interleukin (IL)-33 is a member of the IL-1 family. Serum levels of IL-33 are increased in inflammatory bowel diseases (IBD)， suggesting that IL-33 is involved in the pathogenesis of IBD， although its role is not clear. In this study， we investigated the role of IL-33 in the regulation of T-helper (Th) cell and B cell responses in mesenteric lymph nodes (MLN) in mice with dextran sulfate sodium (DSS)-induced colitis. Here， we showed that IL-33-treated mice were susceptible to DSS-induced colitis as compared with PBS-treated mice. The production of spontaneous inflammatory cytokines production by macrophages or dendritic cells (DC) in MLN significantly increased， and the responses of Th2， regulatory T cells (Treg) and regulatory B cells (Breg) were markedly upregulated， while Th1 responses were significantly downregulated in MLN of IL-33-treated mice with DSS-induced colitis. Our results demonstrate that IL-33 contributes to the pathogenesis of DSS-induced colitis in mice by promoting Th2 responses， but suppressing Th1 responses， in MLN. Moreover， IL-33 treatment increased Breg and Treg responses in MLN in mice with DSS-induced colitis. Therefore， modulation of IL-33/ST2 signaling is implicated as a novel biological therapy for inflammatory diseases associated with Th1 responses.