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Hepatitis C virus-induced myeloid-derived suppressor cells regulate T cell differentiation and function via the STAT3 pathway.

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Ren JP, Zhao J, Dai J, Griffin JW, Wang L, Wu XY, Morrison ZD, Li GY, Ei Gazzar M, Ning SB, Moorman JP, Yao ZQ,


Ren JP, Zhao J, Dai J, Griffin JW, Wang L, Wu XY, Morrison ZD, Li GY, Ei Gazzar M, Ning SB, Moorman JP, Yao ZQ, (click to view)

Ren JP, Zhao J, Dai J, Griffin JW, Wang L, Wu XY, Morrison ZD, Li GY, Ei Gazzar M, Ning SB, Moorman JP, Yao ZQ,

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Immunology 2016 5 5() doi 10.1111/imm.12616

Abstract

T cells play a pivotal role in controlling viral infection; however, the precise mechanisms responsible for regulating T cell differentiation and function during infections are incompletely understood. In this study, we demonstrated an expansion of myeloid-derived suppressor cells (MDSCs), in particular the monocytic MDSCs (M-MDSCs; CD14(+) CD33(+) CD11b(+) HLA-DR(-/low) ), in patients with chronic hepatitis C virus (HCV) infection. Notably, HCV-induced M-MDSCs express high levels of phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and interleukin-10 (IL-10) compared to healthy subjects (HS). Blocking STAT3 signaling reduced HCV-mediated M-MDSC expansion and decreased IL-10 expression. Importantly, we observed a significant increase in the numbers of CD4(+) CD25(+) Foxp3(+) T regulatory (Treg) cells following incubation of healthy peripheral blood mononuclear cells (PBMCs) with MDSCs derived from HCV-infected patients or treated with HCV core protein. In addition, depletion of MDSCs from PBMCs led to a significant reduction of Foxp3(+) Treg cells developed during chronic HCV infection. Moreover, depletion of MDSCs from PBMCs significantly increased IFN-γ production by CD4(+) T effector (Teff) cells derived from HCV patients. These results suggest that HCV-induced MDSCs promote Treg cell development and inhibit Teff cell function, suggesting a novel mechanism for T cell regulation and a new strategy for immunotherapy against human viral diseases. This article is protected by copyright. All rights reserved.

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