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J Am Soc Nephrol. 2015 Sep;26(9):2183-97. doi: 10.1681/ASN.2014050468. Epub 2015 Jan 7.

Role of Myeloid-Derived Suppressor Cells in Glucocorticoid-Mediated Amelioration of FSGS.

Author information

1
State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology, Nanjing, China;
2
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
3
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.
4
Center for Inflammation, Immunity and Infection, Department of Biology, Georgia State University, Atlanta, Georgia.
5
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.
6
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.
7
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.

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.

KEYWORDS:

cell activation; chemokine; focal segmental glomerulosclerosis; lymphocytes; renal protection

PMID:
25568177
PMCID:
PMC4552109
DOI:
10.1681/ASN.2014050468
[Indexed for MEDLINE]
Free PMC Article

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