title: Role of Myeloid-Derived Suppressor Cells in Glucocorticoid-Mediated Amelioration of FSGS.
abstract: The mechanism by which glucocorticoids alleviate renal inflammatory disorders remains incompletely understood. Here, we report that the efficacy of glucocorticoids in ameliorating FSGS depends on the capacity to expand myeloid-derived suppressor cells (MDSCs). After glucocorticoid treatment, the frequency of CD11b(+)HLA-DR(-)CD14(-)CD15(+) MDSCs in peripheral blood rapidly increased in patients with glucocorticoid-sensitive FSGS but remained unchanged in patients with glucocorticoid-resistant FSGS. The frequency of CD11b(+)Gr-1(+) MDSCs in mouse peripheral blood, bone marrow, spleen, kidney-draining lymph nodes (KDLNs), and kidney also increased after glucocorticoid treatment. The induced MDSCs from glucocorticoid-treated mice strongly suppressed T cells, dendritic cells, and macrophages but induced regulatory T cells in spleen, KDLNs, and kidney. Moreover, glucocorticoid treatment suppressed doxorubicin-induced T cell proliferation, dendritic cell and macrophage infiltration, and proinflammatory cytokine production, whereas this protective effect was largely abolished by depleting MDSCs using anti-Gr-1 antibody. Finally, the adoptive transfer of induced MDSCs into the doxorubicin-treated mice not only confirmed the protective role of MDSCs in doxorubicin-induced renal injury but also showed that the transferred MDSCs rapidly migrated into the lymphocyte-accumulating organs, such as the spleen and KDLNs, where they suppressed T cell proliferation. Taken together, these results demonstrate that glucocorticoid treatment ameliorates FSGS by expanding functional MDSCs and that this rapid elevation of MDSCs in peripheral blood may serve as an indicator for predicting the efficacy of glucocorticoid treatment.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology, Nanjing, China;
authors.forename: Limin
authors.initials: L
authors.lastname: Li
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology, Nanjing, China;
authors.forename: Wenli
authors.initials: W
authors.lastname: Diao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology, Nanjing, China;
authors.forename: Fangfang
authors.initials: F
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology, Nanjing, China; Center for Inflammation, Immunity and Infection, Department of Biology, Georgia State University, Atlanta, Georgia.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Jiao
authors.initials: J
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology, Nanjing, China;
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology, Nanjing, China;
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Cai-Hong
authors.initials: CH
authors.lastname: Zeng
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Ming-Chao
authors.initials: MC
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Shaoshan
authors.initials: S
authors.lastname: Liang
authors.affiliation: Center for Inflammation, Immunity and Infection, Department of Biology, Georgia State University, Atlanta, Georgia.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology, Nanjing, China; liuzhihong@nju.edu.cn kzen@nju.edu.cn cyzhang@nju.edu.cn.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and liuzhihong@nju.edu.cn kzen@nju.edu.cn cyzhang@nju.edu.cn.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology, Nanjing, China; National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and liuzhihong@nju.edu.cn kzen@nju.edu.cn cyzhang@nju.edu.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
mesh_terms: D000293:Adolescent; D019264:Adoptive Transfer; D000328:Adult; D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D039481:CD11b Antigen / Q000032:analysis; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D005938:Glucocorticoids / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007668:Kidney / Q000473:pathology; D016256:Lewis X Antigen / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008198:Lymph Nodes / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D022423:Myeloid Cells / Q000737:chemistry / Q000187:drug effects*; D019707:Receptors, Chemokine / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; D005938:Glucocorticoids; C503133:Gr-1 protein, mouse; D006684:HLA-DR Antigens; D016256:Lewis X Antigen; D018950:Lipopolysaccharide Receptors; C494192:Ly-6C antigen, mouse; D019707:Receptors, Chemokine; D004317:Doxorubicin
keywords: cell activation; chemokine; focal segmental glomerulosclerosis; lymphocytes; renal protection