title: MicroRNA-146a feedback suppresses T cell immune function by targeting Stat1 in patients with chronic hepatitis B.
abstract: More than 350 million people are chronically infected with hepatitis B virus, and dysfunctional T cell responses contribute to persistent viral infection and immunopathogenesis in chronic hepatitis B (CHB). However, the underlying mechanisms of T cell hyporesponsiveness remain largely undefined. Given the important role of microRNA-146a (miR-146a) in diverse aspects of lymphocyte function, we investigated the potential role and mechanism of miR-146a in regulating T cell immune responses in CHB. We found that miR-146a expression in T cells is significantly upregulated in CHB compared with healthy controls, and miR-146a levels were correlated with serum alanine aminotransaminase levels. Both inflammatory cytokines and viral factors led to miR-146a upregulation in T cells. Stat1 was identified as a miR-146a target that is involved in antiviral cytokine production and the cytotoxicity of CD4(+) and CD8(+) T cells. In vitro blockage of miR-146a in T cells in CHB greatly enhanced virus-specific T cell activity. Therefore, our work demonstrates that miR-146a upregulation in CHB causes impaired T cell function, which may contribute to immune defects and immunopathogenesis during chronic viral infection.
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Saifeng
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Ju
authors.forename: Bao
authors.initials: B
authors.lastname: Zhao
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yan
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Lebing
authors.initials: L
authors.lastname: Yang
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Ma
authors.forename: Lizhao
authors.initials: L
authors.lastname: Chen
authors.forename: Yali
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Duan
authors.forename: Xinyue
authors.initials: X
authors.lastname: Chen
authors.forename: Songdong
authors.initials: S
authors.lastname: Meng
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D057809:HEK293 Cells; D056945:Hep G2 Cells; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019169:Jurkat Cells; D035683:MicroRNAs / Q000502:physiology*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human