机构：[1]Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA[2]Virginia Commonwealth University Institute of Molecular Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA[3]Virginia Commonwealth University Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA[4]Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China[5]Institute of Immunology, First Bethune Hospital of Jilin University, Changchun, Jilin, China[6]Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China[7]Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
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.
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 naïve CD4+ T cells under Th17-polarising conditions.
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)-1β, TNF-α). 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.
Our studies suggest that proinflammatory MDSCs with their capacity to drive Th17 cell differentiation may be a critical pathogenic factor in autoimmune arthritis.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
基金：
The present study was supported in part by National Institutes of Health
(NIH) Grants CA175033 and CA154708 (X-YW), the Natural Science Foundation of
China (81302554 to FH, 81030057 to ZL and 81173456 to JL), 973 Program of
China (2010CB529100, ZL), and Peking University People’s Hospital Research and
Development Fund (RDB2013-04, FH). Flow cytometry facility was supported in part
by NCI Cancer Center Support Grant to VCU Massey Cancer Center P30CA16059.
X-YW is the Harrison Endowed Scholar in Cancer Research.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2015]版：
大类|1 区医学
小类|1 区风湿病学
最新[2025]版：
大类|1 区医学
小类|1 区风湿病学
第一作者：
第一作者机构：[1]Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA[2]Virginia Commonwealth University Institute of Molecular Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA[3]Virginia Commonwealth University Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
共同第一作者：
通讯作者：
通讯机构：[1]Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA[2]Virginia Commonwealth University Institute of Molecular Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA[3]Virginia Commonwealth University Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA[4]Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China[*1]Department of Human & Molecular Genetics, Virginia Commonwealth University School of Medicine, PO Box 980033, Richmond, VA 23298, USA[*2]Department of Rheumatology and Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China
推荐引用方式(GB/T 7714)：
Chunqing Guo,Fanlei Hu,Huanfa Yi,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):278-85.doi:10.1136/annrheumdis-2014-205508.
APA：
Chunqing Guo,Fanlei Hu,Huanfa Yi,Zhitao Feng,Changzheng Li...&Xiang-Yang Wang.(2016).Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis..Annals of the rheumatic diseases,75,(1)
MLA：
Chunqing Guo,et al."Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis.".Annals of the rheumatic diseases 75..1(2016):278-85
医学