Recent evidence indicates the existence of subpopulations of myeloid-derived suppressor cells (MDSCs) with distinct phenotypes and functions. Here, we characterized the role of MDSC subpopulations in the pathogenesis of autoimmune arthritis in a collagen-induced arthritis (CIA) mouse model. The splenic CD11b + Gr-1 + MDSC population expanded in CIA mice, and these cells could be subdivided into polymorphonuclear (PMN) and mononuclear (MO) MDSC subpopulations based on Ly6C and Ly6G expression. During CIA, the proportion of splenic MO-MDSCs was increased in association with the severity of joint inflammation, while PMN-MDSCs were decreased. MO-MDSCs expressed higher levels of surface CD40 and CD86 protein, but lower levels of Il10, Tgfb1, Ccr5, and Cxcr2 mRNA. PMN-MDSCs exhibited a more potent capacity to suppress polyclonal T-cell proliferation in vitro, compared with MO-MDSCs. Moreover, the adoptive transfer of PMN-MDSCs, but not MO-MDSCs, decreased joint inflammation, accompanied by reduced levels of serum cytokine secretion and the frequencies of Th1 and Th17 cells in draining lymph nodes. These results suggest that there could be a shift from potently suppressive PMN-MDSCs to poorly suppressive MO-MDSCs during the development of experimental arthritis, which might reflect the failure of expanded MDSCs to suppress autoimmune arthritis.Keywords: Collagen-induced arthritis r Myeloid-derived suppressor cells r Rheumatoid arthritis r T cells Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionMyeloid-derived suppressor cells (MDSCs), defined according to their origin and function, were initially identified as a Correspondence: Dr. Zhijun Jiao e-mail: jiaozhijun@ujs.edu.cn heterogeneous population of immature cells derived from myeloid progenitors with immune-suppressive functions in tumor-bearing hosts [1][2][3]. In mice, MDSCs are broadly defined as CD11b + Gr-1 + cells, while in humans, MDSCs are commonly characterized as CD11b + CD33 + CD14 − HLA-DR- [4,5] phenotypes, morphologies, and, importantly, immunosuppressive mechanisms in humans and mice. Although a critical role of MDSCs in antitumor immunity has been well defined, emerging evidence indicates a role in the regulation of autoimmune pathology. Recent studies have shown the expansion of MDSCs in several mouse models of autoimmune diseases, including rheumatoid arthritis (RA) [7][8][9], multiple sclerosis [10][11][12][13][14], inflammatory bowel disease [15,16], uveoretinitis [17], alopecia areata [18], and type 1 diabetes [19,20]. These data strongly suggest a regulatory role for MDSCs in autoimmune conditions. However, the specific contribution of MDSCs and MDSC subpopulations to the pathological processes associated with inflammatory autoimmune abnormalities remains unknown.RA is a chronic inflammatory autoimmune disease of the synovial joints that is characterized by leukocyte infiltration and synoviocyte activation, leading to cartilage and bone destruction [21]. In previous st...

The outstanding characteristics of circulatory microRNAs (miRNAs) attract much attention in research on disease biomarkers and disease pathogenesis. This study aimed to identify the expression profiles of plasma miRNAs in patients with rheumatoid arthritis (RA). Thirty-three miRNAs were screened using an miRNA array, of which 9 miRNAs were validated as differentially expressed in the plasma of RA patients compared with healthy controls (HCs). miRNA-4634 (miR-4634), miR-181d and miR-4764-5p expression levels were increased, whereas miR-342-3p, miR-3926, miR-3925-3p, miR-122-3p, miR-9-5p and miR-219-2-3p expression levels were decreased in RA patients. The areas under the curve (AUCs) were generated to estimate the sensitivity and specificity of each miRNA or the panel of all 9 miRNAs as biomarkers for RA. AUCs for 9 individual miRNAs ranged from 0.6254 to 0.818; however, the AUC for the panel of 9 miRNAs reached 0.964. Levels of miR-122-3p, miR-3925-3p, miR-342-3p and miR-4764-5p expression showed significant differences between RA and other control groups. miR-4764-5p, miR-4634, miR-9-5p and miR-219-2-3p exhibited significant correlations with either plasma cytokine and chemokine levels or clinical features. In conclusion, this study identified 9-plasma miRNAs signature in Chinese patients with RA which may serve as noninvasive biomarkers for the diagnosis of RA.