期刊
NATURE MEDICINE
卷 18, 期 7, 页码 1077-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2815
关键词
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资金
- National Natural Science Foundation of China and 973 program [30930084, 2010CB529705, 91029708, 30871298]
- Chinese Academy of Sciences [KSCX2-YW-R-146]
- Science and Technology Commission of Shanghai Municipality [10JC1416600]
- National Natural Science Foundation of China [30971632, 81025016]
- Chinese Ministry of Health [201202008]
- Program of the Shanghai Commission of Science and Technology [10JC1409300]
Inflammatory cytokines such as interleukin-17 (IL-17) promote inflammatory autoimmune diseases. Although several microRNAs (miRNAs) have been shown to regulate autoimmune pathogenesis by affecting lymphocyte development and function, the role of miRNAs in resident cells present in inflammatory lesions remains unclear. Here we show that miR-23b is downregulated in inflammatory lesions of humans with lupus or rheumatoid arthritis, as well as in the mouse models of lupus, rheumatoid arthritis or multiple sclerosis. IL-17 downregulates miR-23b expression in human fibroblast-like synoviocytes, mouse primary kidney cells and astrocytes and is essential for the downregulation of miR-23b during autoimmune pathogenesis. In turn, miR-23b suppresses IL-17-, tumor necrosis factor alpha (TNF-alpha)- or IL-1 beta-induced NF-kappa B activation and inflammatory cytokine expression by targeting TGF-beta-activated kinase 1/MAP3K7 binding protein 2 (TAB2), TAB3 and inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-alpha) and, consequently, represses autoimmune inflammation. Thus, IL-17 contributes to autoimmune pathogenesis by suppressing miR-23b expression in radio-resident cells and promoting proinflammatory cytokine expression.
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