HCV-induced miR146a Controls SOCS1/STAT3 and Cytokine Expression in Monocytes to Promote Regulatory T-cell Development
Host innate and adaptive immune responses must be tightly regulated by an intricate balance between positive and negative signals to ensure their appropriate onset and termination while fighting pathogens and avoiding autoimmunity; persistent pathogens may usurp these regulatory machineries to dampen host immune responses for their persistence in vivo. Here, we demonstrate that miR146a is up‐regulated in monocytes from hepatitis C virus (HCV )‐infected individuals compared to control subjects. Interestingly, miR146a expression in monocytes without HCV infection increased, whereas its level in monocytes with HCV infection decreased, following Toll‐like receptor (TLR ) stimulation. This miR146a induction by HCV infection and differential response to TLR stimulation were recapitulated in vitro in monocytes co‐cultured with hepatocytes with or without HCV infection. Importantly, inhibition of miR146a in monocytes from HCV ‐infected patients led to a decrease in IL ‐23, IL ‐10 and TGF ‐β expressions through the induction of suppressor of cytokine signalling 1 (SOCS 1) and the inhibition of signal transducer and activator transcription 3 (STAT 3), and this subsequently resulted in a decrease in regulatory T cells (Tregs) accumulated during HCV infection. These results suggest that miR146a may regulate SOCS 1/STAT 3 and cytokine signalling in monocytes, directing T‐cell differentiation and balancing immune clearance and immune injury during chronic viral infection.
Ren, Junping; Ying, Rue S.; Cheng, Yong Q.; Wang, Ling; El Gazzar, Mohamed A.; Li, Guang Y.; Ning, Shun B.; Moorman, Jonathon P.; and Yao, Zhi Q.. 2016. HCV-induced miR146a Controls SOCS1/STAT3 and Cytokine Expression in Monocytes to Promote Regulatory T-cell Development. Journal of Viral Hepatitis. Vol.23(10). 755-766. https://doi.org/10.1111/jvh.12537 ISSN: 1352-0504
This document is an author manuscript from PMC. The publisher's final edited version of this article is available at Journal of Viral Hepatitis .