Functional characterization of myeloid‐derived suppressor cell subpopulations during the development of experimental arthritis

• Published in: European journal of immunology 2015-02, Vol.45 (2), p.464-473
• Main Authors: Wang, Wenhong, Jiao, Zhijun, Duan, Tanghai, Liu, Meihong, Zhu, Bo, Zhang, Yingying, Xu, Qiugui, Wang, Rui, Xiong, Yuyun, Xu, Huaxi, Lu, Liwei
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antigens, Ly - genetics; Antigens, Ly - immunology; Arthritis; Arthritis, Experimental - genetics; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; B7-2 Antigen - genetics; B7-2 Antigen - immunology; CD11b Antigen - genetics; CD11b Antigen - immunology; CD40 Antigens - genetics; CD40 Antigens - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cell Lineage - immunology; Cell Proliferation; Collagen‐induced arthritis; Gene Expression; Immunophenotyping; Joints - immunology; Joints - pathology; Leukocytes; Lymph Nodes - immunology; Lymph Nodes - pathology; Male; Medical research; Mice; Mice, Inbred DBA; Myeloid Cells - immunology; Myeloid Cells - pathology; Myeloid Cells - transplantation; Myeloid‐derived suppressor cells; Receptors, Chemokine - genetics; Receptors, Chemokine - immunology; Rheumatoid arthritis; Rodents; Spleen - immunology; Spleen - pathology; T cells; Th1 Cells - immunology; Th1 Cells - metabolism; Th1 Cells - pathology; Th17 Cells - immunology; Th17 Cells - metabolism; Th17 Cells - pathology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201444799

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.