IL-33, a branded ‘Th2’ cytokine, could accelerate the Th1-mediated colitis under an IL-10 deficient condition.
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IL-10 sufficient mice were protected from the IL-33-mediated mucosal inflammation.
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IL-33 induced a phenotypically unique subset of IL-10-producing regulatory B cells (BregIL-33).
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Adoptive transfer of BregIL-33 blocked the spontaneous colitis in IL-10-deficient mice (therapeutic potential).
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Our findings offer new insights into the immunological mechanisms underlying mucosal inflammation, and its regulation.
Abstract
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+CD1dhiIgMhiCD5-CD23-Tim-1-) of IL-10 producing Breg-like cells (BregIL-33) was identified responsible for the protection. We demonstrated further that BregIL-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 BregIL-33 against mucosal inflammatory disorders in the gut.