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髓源性抑制细胞具有促炎作用,并通过调控辅助性T细胞17(Th17)分化来调节胶原诱导的关节炎。

Myeloid-derived suppressor cells are proinflammatory and regulate collagen-induced arthritis through manipulating Th17 cell differentiation.

作者信息

Zhang Hui, Wang Shuang, Huang Yuefang, Wang Hongyue, Zhao Jijun, Gaskin Felicia, Yang Niansheng, Fu Shu Man

机构信息

Department of Rheumatology, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou 510080, China.

Department of Pediatrics, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou 510080, PR China.

出版信息

Clin Immunol. 2015 Apr;157(2):175-86. doi: 10.1016/j.clim.2015.02.001. Epub 2015 Feb 11.

Abstract

Myeloid-derived suppressor cells (MDSC) and Th17 cells were found to expand in collagen-induced arthritis (CIA) significantly. Two subsets of MDSC, polymorphonuclear (PMN) and mononuclear (MO), were detected and their ratios varied during the development of CIA. The depletion of MDSC in vivo resulted in suppression of T-cell proliferation and decreased IL-17A and IL-1β production. The adoptive transfer of MDSC restored the severity of arthritis and Th17 cell differentiation. The depletion of MDSCs on day 35 resulted in arthritis amelioration without reaching a significant difference. Furthermore, MDSCs from CIA mice had higher production of IL-1β and promoted Th17 cell differentiation. The expansion of MDSCs in the peripheral blood of rheumatoid arthritis (RA) patients was in correlation with increased Th17 cells and disease activity DAS28. These results support the hypothesis that MDSC may play a significant proinflammatory role in the pathogenesis of CIA and RA by inducing Th17 development in an IL-1β-dependent manner.

摘要

研究发现,髓源性抑制细胞(MDSC)和Th17细胞在胶原诱导的关节炎(CIA)中显著扩增。检测到MDSC的两个亚群,即多形核(PMN)和单核(MO)亚群,且它们的比例在CIA发展过程中有所变化。体内MDSC的耗竭导致T细胞增殖受到抑制,白细胞介素-17A(IL-17A)和白细胞介素-1β(IL-1β)的产生减少。MDSC的过继转移恢复了关节炎的严重程度和Th17细胞分化。在第35天耗竭MDSC导致关节炎改善,但未达到显著差异。此外,来自CIA小鼠的MDSC产生更高水平的IL-1β,并促进Th17细胞分化。类风湿关节炎(RA)患者外周血中MDSC的扩增与Th17细胞增加及疾病活动度DAS28相关。这些结果支持以下假说:MDSC可能通过以IL-1β依赖的方式诱导Th17细胞发育,在CIA和RA的发病机制中发挥重要的促炎作用。

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