IL-10-producing regulatory B cells induced by IL-33 (BregIL-33) effectively attenuate mucosal inflammatory responses in the gut
| Autor: | Andreas Romaine, Damo Xu, Yu-Lung Lau, Hongzhi Zhao, Hermelijn H. Smits, Marina Botto, Guangsheng Ling, Susanne Sattler, Foo Y. Liew, Talat H. Malik, Liliane Fossati-Jimack, Leonie Hussaarts, Fang-Ping Huang, H. Terence Cook |
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| Rok vydání: | 2014 |
| Předmět: |
BregIL-33
IL-33-induced/expanded Breg Adoptive cell transfer Mucosal inflammation Breg regulatory B cell Regulatory B cells IBD Immunology Gene Expression Biology Lymphocyte Activation Inflammatory bowel disease Article Mice Antigens CD medicine Animals Immunology and Allergy IL-2 receptor Mice Knockout B-Lymphocytes Regulatory IBD inflammatory bowel disease Interleukins Regulatory B cell Interleukin Peripheral tolerance Colitis Interleukin-33 medicine.disease Adoptive Transfer Interleukin-10 Interleukin 33 Interleukin 10 Gastric Mucosa IL-10 IL-33 Female Injections Intraperitoneal |
| Zdroj: | Journal of Autoimmunity, 50, 107-122 Journal of Autoimmunity |
| ISSN: | 0896-8411 |
| DOI: | 10.1016/j.jaut.2014.01.032 |
| Popis: | 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. 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 (BregIL-33). • Adoptive transfer of BregIL-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. |
| Databáze: | OpenAIRE |
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