Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis. Issue 1 (4th November 2014)

• Record Type: Journal Article
• Authors: Guo, Chunqing; Hu, Fanlei; Yi, Huanfa; Feng, Zhitao; Li, Changzheng; Shi, Lianjie; Li, Yingni; Liu, Hongjiang; Yu, Xiaofei; Wang, Hongxia; Li, Juan; Li, Zhanguo; Wang, Xiang-Yang
• Is Part Of: Annals of the rheumatic diseases. Volume 75:Issue 1(2016)
• Page Start: 278
• Page End: 285
• Publication Date: 2014-11-04
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-205508
• Languages: English
• ISSNs: 0003-4967

Abstract

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