Regulatory B cells (Breg) have attracted increasing attention for their roles in maintaining peripheral tolerance. Interleukin 33 (IL-33) is a recently identified IL-1 family member, which leads a double-life with both pro- and anti-inflammatory properties. We report here that peritoneal injection of IL-33 exacerbated inflammatory bowel disease in IL-10-deficient (IL-10 −/− ) mice, whereas IL-33-treated IL-10-sufficient (wild type) mice were protected from the disease induction. A phenotypically unconventional subset(s) (CD19 + CD25 + CD1d hi IgM hi CD5 – CD23 – Tim-1 – ) of IL-10 producing Breg-like cells (Breg IL-33 ) was identified responsible for the protection. We demonstrated further that Breg IL-33 isolated from these mice could suppress immune effector cell expansion and functions and, upon adoptive transfer, effectively blocked the development of spontaneous colitis in IL-10 −/− mice. Our findings indicate an essential protective role, hence therapeutic potential, of Breg IL-33 against mucosal inflammatory disorders in the gut. Highlights • IL-33, a branded ‘Th2’ cytokine, could accelerate the Th1-mediated colitis under an IL-10 deficient condition. • IL-10 sufficient mice were protected from the IL-33-mediated mucosal inflammation. • IL-33 induced a phenotypically unique subset of IL-10-producing regulatory B cells (Breg IL-33 ). • Adoptive transfer of Breg IL-33 blocked the spontaneous colitis in IL-10-deficient mice (therapeutic potential). • Our findings offer new insights into the immunological mechanisms underlying mucosal inflammation, and its regulation.
【저자키워드】 IL-33, IL-10, IBD, IBD, Inflammatory bowel disease, Regulatory B cell, Mucosal inflammation, Breg, regulatory B cell, BregIL-33, IL-33-induced/expanded Breg,