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The reduction of miR146b-5p in monocytes and T cells could contribute to the immunopathogenesis of hepatitis C virus infection.

ABSTRACT: It has been reported that various kinds of miRNAs could affect the pathogenesis of hepatitis C virus infection. Recently, our group reported that deep-sequencing analysis was useful to detect disease-specific miRNAs. The aim of this study is to identify the HCV-specific miRNAs that could contribute to the immunopathogenesis of HCV by using clinical samples and in vitro analysis. Five miRNAs (hsa-miR181a-2-3p, hsa-miR-374a-3p, hsa-miR374a-5p, hsa-miR-204-5p and hsa-miR146b-5p) were shown to be significantly downregulated in CH-C by deep sequence analysis. The average ratio (PBMCs miRNAs/serum miRNAs) of hsa-miR146b-5p was highest among all the miRNAs. Moreover, serum hsa-miR146b-5p was significantly down-regulated in CH-C patients in comparison to CH-B patients and healthy subjects. The expression of hsa-miR146b-5p in CD3⁺ T cells and CD14⁺ monocytes of CH-C patients was significantly lower than that of the other groups. The hsa-miR146b-5p expression in CD14⁺ monocytes of SVR patients treated with Peg-IFN/RBV was significantly higher than in those of non-SVR patients treated with Peg IFN/RBV. However, the hsa-miR146b-5p expression in CD14⁺ monocytes of SVR patients treated with DCV and ASV was comparable to that in monocytes of non-SVR patients treated with DCV and ASV. Moreover, the expression levels of hsa-miR146b-5p in CD14⁺ monocytes were significantly increased after achieving SVR and 1(OH)Vitamin D3 treatment. Further, the expression of HCV-Core could suppress miR146b-5p expression in immune cells and affect the expression of various kinds of cytokines by affecting the NF-?B signaling. In conclusion, the reduction of miR146b-5p in monocytes and T cells could contribute to the immunopathogenesis of hepatitis C virus infection.

SUBMITTER: Kondo Y

PROVIDER: S-EPMC6746729 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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The reduction of miR146b-5p in monocytes and T cells could contribute to the immunopathogenesis of hepatitis C virus infection.

Kondo Yasuteru Y Kogure Takayuki T Ninomiya Masashi M Fukuda Ryo R Monma Norikazu N Ikeo Kazuho K Tanaka Yasuhito Y

Scientific reports 20190916 1

It has been reported that various kinds of miRNAs could affect the pathogenesis of hepatitis C virus infection. Recently, our group reported that deep-sequencing analysis was useful to detect disease-specific miRNAs. The aim of this study is to identify the HCV-specific miRNAs that could contribute to the immunopathogenesis of HCV by using clinical samples and in vitro analysis. Five miRNAs (hsa-miR181a-2-3p, hsa-miR-374a-3p, hsa-miR374a-5p, hsa-miR-204-5p and hsa-miR146b-5p) were shown to be si ...[more]

PMID: 31527804

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Project description:Background & aimsThe hepatitis D virus (HDV) causes the most severe form of chronic hepatitis, often progressing to cirrhosis within 5 to 10 years. There is no curative treatment, and the mechanisms underlying the accelerated liver disease progression are unknown.MethodsInnate and adaptive immune responses were studied in blood and liver of 24 patients infected with HDV and 30 uninfected controls by multiparameter flow cytometry in correlation with disease severity and stage.ResultsThe 2 main intrahepatic innate immune-cell populations, mucosal-associated invariant T cells and natural killer (NK) cells, were reduced in the livers of patients infected with HDV compared with those of uninfected controls but were more frequently activated in the liver compared with the blood. Most intrahepatic cluster of differentiation (CD) 8-positive (CD8+) T cells were memory cells or terminal effector memory cells, and most of the activated and degranulating (CD107a+) HDV-specific and total CD8+ T cells were liver-resident (CD69+C-X-C motif chemokine receptor 6+). Unsupervised analysis of flow cytometry data identified an activated, memory-like, tissue-resident HDV-specific CD8+ T-cell cluster with expression of innate-like NK protein 30 (NKp30) and NK group 2D (NKG2D) receptors. The size of this population correlated with liver enzyme activity (r = 1.0). NKp30 and NKG2D expression extended beyond the HDV-specific to the total intrahepatic CD8+ T-cell population, suggesting global bystander activation. This was supported by the correlations between (i) NKG2D expression with degranulation of intrahepatic CD8+ T cells, (ii) frequency of degranulating CD8+ T cells with liver enzyme activity and the aspartate aminotransferase-to-platelet ratio index score, and by the in vitro demonstration of cytokine-induced NKG2D-dependent cytotoxicity.ConclusionAntigen-nonspecific activation of liver-resident CD8+ T cells may contribute to inflammation and disease stage in HDV infection.

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The reduction of miR146b-5p in monocytes and T cells could contribute to the immunopathogenesis of hepatitis C virus infection.

Publications

The reduction of miR146b-5p in monocytes and T cells could contribute to the immunopathogenesis of hepatitis C virus infection.

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