HCV-associated exosomes promote myeloid-derived suppressor cell expansion via inhibiting miR-124 to regulate T follicular cell differentiation and function

Cell Discovery
Lin WangZhi Q Yao

Abstract

Virus-infected cells can regulate non-permissive bystander cells, but the precise mechanisms remain incompletely understood. Here we report that this process can be mediated by transfer of viral RNA-loaded exosomes shed from infected cells to myeloid-derived suppressor cells (MDSCs), which in turn regulate the differentiation and function of T cells during viral infection. Specifically, we demonstrated that patients with chronic hepatitis C virus (HCV) infection exhibited significant increases in T follicular regulatory (TFR) cells and decreases in T follicular helper (TFH) cells. These MDSC-mediated T-cell dysregulations resulted in an increased ratio of TFR/TFH and IL-10 production in peripheral blood. Specifically, co-culture of MDSCs derived from HCV patients with healthy peripheral blood mononuclear cells (PBMCs) induced expansion of TFR, whereas depletion of MDSCs from PBMCs of HCV patients reduced the increases in TFR frequency and IL-10 production, and promoted the differentiation of IFN-γ-producing TFH cells. Importantly, we found that exosomes isolated from the plasma of HCV patients and supernatant of HCV-infected hepatocytes could drive monocytic myeloid cell differentiation into MDSCs. These exosomes were enriched ...Continue Reading

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Citations

Jul 10, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Alexandre BalaphasLeo Hans Bühler
Mar 22, 2019·Frontiers in Immunology·Jordi OchandoEstela Paz-Artal
Nov 6, 2020·PLoS Computational Biology·Carolin ZitzmannAlan S Perelson
May 11, 2021·Frontiers in Immunology·Waqas AhmedHameeda Sultana
Nov 11, 2021·Journal of Leukocyte Biology·Mrigya Babuta, Gyongyi Szabo

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Methods Mentioned

BETA
flow cytometry
confocal microscopy
gene array
transfection
PCR

Software Mentioned

Prism
FlowJo

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