Immunology 2016 Oct 18() doi 10.1111/imm.12680
Myeloid-derived suppressor cells (MDSCs) and microRNAs (miRNAs) contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood. We have recently shown marked expansion of MDSCs that promote regulatory T (Treg) cell development in patients with chronic hepatitis C virus (HCV) infection. Here we further investigated whether the HCV-induced expansion of MDSCs and Tregs is regulated by a miRNA-mediated mechanism. miRNA array analysis revealed that six miRNAs were up-regulated and six miRNAs were down-regulated significantly in myeloid cells during HCV infection. Real-time RT-PCR confirmed the down-regulation of miR-124 in MDSCs from HCV patients. Bioinformatic analysis suggested that miR-124 may be involved in the regulation of signal transducer and activator of transcription 3 (STAT-3), which was overexpressed in MDSCs from HCV patients. Notably, silencing of STAT-3 significantly increased the miR-124 expression, whereas reconstituting miR-124 decreased the levels of STAT-3, as well as IL-10 and TGF-β, which were overexpressed in MDCSs, and reduced the frequencies of Foxp3(+) Treg cells that were developed during chronic HCV infection. These results suggest that reciprocal regulation of miR-124 and STAT-3 in MDSCs promotes Treg cell development, thus uncovering a novel mechanism for the expansion of MDSC and Treg cells during HCV infection. This article is protected by copyright. All rights reserved.