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学科主题: 临床医学
题名:
Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis
作者: Guo, Chunqing1,2,3; Hu, Fanlei4; Yi, Huanfa1,2,3,5; Feng, Zhitao6,7; Li, Changzheng6,7; Shi, Lianjie4; Li, Yingni4; Liu, Hongjiang4; Yu, Xiaofei1,2,3; Wang, Hongxia1,2,3; Li, Juan6,7; Li, Zhanguo4; Wang, Xiang-Yang1,2,3
刊名: ANNALS OF THE RHEUMATIC DISEASES
发表日期: 2016
DOI: 10.1136/annrheumdis-2014-205508
卷: 75, 期:1, 页:278-285
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Rheumatology
研究领域[WOS]: Rheumatology
关键词[WOS]: COLLAGEN-INDUCED ARTHRITIS ; TH17 CELLS ; RHEUMATOID-ARTHRITIS ; T-CELLS ; IMMUNE-SYSTEM ; DISEASE ; INTERLEUKIN-17 ; MICE ; INDUCTION ; PLAY
英文摘要:

Objectives Although myeloid-derived suppressor cells (MDSCs) have been linked to T cell tolerance, their role in autoimmune rheumatoid arthritis (RA) remains elusive. Here we investigate the potential association of MDSCs with the disease pathogenesis using a preclinical model of RA and specimen collected from patients with RA.

Methods The frequency of MDSCs in blood, lymphoid tissues, inflamed paws or synovial fluid and their association with disease severity, tissue inflammation and the levels of pathogenic T helper (Th) 17 cells were examined in arthritic mice or in patients with RA (n=35) and osteoarthritis (n=15). The MDSCs in arthritic mice were also characterised for their phenotype, inflammation status, T cell suppressive activity and their capacity of pro-Th17 cell differentiation. The involvement of MDSCs in the disease pathology and a Th17 response was examined by adoptive transfer or antibody depletion of MDSCs in arthritic mice or by coculturing mouse or human MDSCs with naive CD4+T cells under Th17-polarising conditions.

Results MDSCs significantly expanded in arthritic mice and in patients with RA, which correlated positively with disease severity and an inflammatory Th17 response. While displaying T cell suppressive activity, MDSCs from arthritic mice produced high levels of inflammatory cytokines (eg, interleukin (IL)-1 beta, TNF-alpha). Mouse and human MDSCs promoted Th17 cell polarisation ex vivo. Transfer of MDSCs facilitated disease progression, whereas their elimination in arthritic mice ameliorated disease symptoms concomitant with reduction of IL-17A/Th17 cells.

Conclusions Our studies suggest that proinflammatory MDSCs with their capacity to drive Th17 cell differentiation may be a critical pathogenic factor in autoimmune arthritis.

语种: 英语
所属项目编号: CA175033 ; CA154708 ; 81302554 ; 81030057 ; 81173456 ; 2010CB529100 ; RDB2013-04 ; P30CA16059
项目资助者: National Institutes of Health (NIH) ; Natural Science Foundation of China ; 973 Program of China ; Peking University People&prime ; s Hospital Research and Development Fund ; NCI Cancer Center Support Grant
WOS记录号: WOS:000366402400037
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66009
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA 23298 USA
2.Virginia Commonwealth Univ, Sch Med, Inst Mol Med, Richmond, VA 23298 USA
3.Virginia Commonwealth Univ, Sch Med, Massey Canc Ctr, Richmond, VA 23298 USA
4.Peking Univ, Peoples Hosp, Dept Rheumatol & Immunol, Beijing 100871, Peoples R China
5.Jilin Univ, Inst Immunol, Bethune Hosp 1, Changchun 130023, Jilin, Peoples R China
6.Southern Med Univ, Nanfang Hosp, Dept Rheumatol, Guangzhou, Guangdong, Peoples R China
7.Southern Med Univ, Sch Tradit Chinese Med, Dept Tradit Chinese Internal Med, Guangzhou, Guangdong, Peoples R China

Recommended Citation:
Guo, Chunqing,Hu, Fanlei,Yi, Huanfa,et al. Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis[J]. ANNALS OF THE RHEUMATIC DISEASES,2016,75(1):278-285.
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