title: Functional characterization of myeloid-derived suppressor cell subpopulations during the development of experimental arthritis.
abstract: 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.
authors.affiliation: Zhenjiang Key Laboratory of Medical Immunology, Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China; Department of Pathogenic Biology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Wang
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Jiao
authors.forename: Tanghai
authors.initials: T
authors.lastname: Duan
authors.forename: Meihong
authors.initials: M
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiugui
authors.initials: Q
authors.lastname: Xu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Yuyun
authors.initials: Y
authors.lastname: Xiong
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation; D015870:Gene Expression; D016130:Immunophenotyping; D007596:Joints / Q000276:immunology / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000950:Antigens, Ly; D051940:B7-2 Antigen; D039481:CD11b Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; C503133:Gr-1 protein, mouse; C494192:Ly-6C antigen, mouse; C480309:Ly6G antigen, mouse; D019707:Receptors, Chemokine
keywords: Collagen-induced arthritis; Myeloid-derived suppressor cells; Rheumatoid arthritis; T cells