Decline of miR‐124 in myeloid cells promotes regulatory T‐cell development in hepatitis C virus infection

Abstract

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 Treg cells is regulated by an miRNA-mediated mechanism. The RNA 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 interleukin-10 and transforming growth factor-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.

The Role of Myeloid-Derived Suppressor Cells in Viral Infection

“…During HCV infection, expression of several miRNAs was altered in CD33 + myeloid cells, including miR-124, which was downregulated, in part, due to HCV-induced overexpression of STAT-3 (127). Downregulation of miR-124 correlated with increased levels of IL-10 and TGF-b expression by MDSCs (127).…”

Analysis of Micro RNA 29, 122 and 155 Gene Expression in Immune Cells of Egyptian Patients with Chronic Hepatitis C Virus Infection

“…Our data showed that MDSC has a positive correlation with miR-122 and 29 in control but has a negative correlation in patients. MiR-29 was significantly decreased in CD33 + myeloid cells from HCV-infected patients compared with healthy participants, revealing a decline in miR-29 expression in myeloid cells in the setting of chronic HCV infection lead to inhibition STAT-3 (Ren et al, 2016).…”

“…MDSCs and miRNAs contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood (Ren et al, 2016). MicroRNAs represent an interesting field of investigation with regards HCV infection and replication.…”

“…MiR-29 has been shown to induce myeloid progenitor expansion. It is possible that aberrant expression of miRNAs contributes to MDSC expansion under pathological conditions (Ren et al, 2016).…”

Roles of microRNAs in T cell immunity: Implications for strategy development against infectious diseases

“…For example, in human immunodeficiency virus (HIV) infection, miR‐155, and miR‐29 were shown to exhibit anti‐HIV‐1 effects by modulating T cell immunity. During hepatitis C virus (HCV) infection in myeloid cells, miR‐124 was shown to be downregulated, which promotes Treg cell development by targeting STAT3; miR‐155 was also shown to be downregulated in NK cells during HCV infections, prompting an increase in IFN‐γ production by regulating Tim‐3 . miR‐17–92 are also considered essential factors in both Th1 and T FH for an effective response against viral infections .…”