HCV-induced miR146a controls SOCS1/STAT3 and cytokine expression in monocytes to promote regulatory T-cell development.

Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 9435672 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2893 (Electronic) Linking ISSN: 13520504 NLM ISO Abbreviation: J Viral Hepat Subsets: MEDLINE

Original Publication: Oxford ; Boston : Blackwell Scientific Publications, 1994-

Cytokines/*biosynthesis ; Hepacivirus/*physiology ; MicroRNAs/*metabolism ; Monocytes/*immunology ; STAT3 Transcription Factor/*biosynthesis ; Suppressor of Cytokine Signaling 1 Protein/*biosynthesis ; T-Lymphocytes, Regulatory/*immunology; Gene Expression Regulation ; Hepacivirus/immunology ; Humans ; Immune Tolerance

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 (SOCS1) and the inhibition of signal transducer and activator transcription 3 (STAT3), and this subsequently resulted in a decrease in regulatory T cells (Tregs) accumulated during HCV infection. These results suggest that miR146a may regulate SOCS1/STAT3 and cytokine signalling in monocytes, directing T-cell differentiation and balancing immune clearance and immune injury during chronic viral infection.
(© 2016 John Wiley & Sons Ltd.)

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R01 AI114748 United States AI NIAID NIH HHS; R01 DK093526 United States DK NIDDK NIH HHS

Keywords: SOCS1; STAT3; hepatitis C virus; miR146a; monocytes; regulatory T cells

0 (Cytokines)
0 (MIRN146 microRNA, human)
0 (MicroRNAs)
0 (SOCS1 protein, human)
0 (STAT3 Transcription Factor)
0 (STAT3 protein, human)
0 (Suppressor of Cytokine Signaling 1 Protein)

Date Created: 20160324 Date Completed: 20171103 Latest Revision: 20240530

20250114

PMC5028233

10.1111/jvh.12537

27004559