ArticleJournal of virology2013
Differential regulation of interleukin-12 (IL-12)/IL-23 by Tim-3 drives T(H)17 cell development during hepatitis C virus infection.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- MicroRNA-155 regulates interferon-γ production in natural killer cells via Tim-3 signalling in chronic hepatitis C virus infection.Immunology · 2015Trial
- Unraveling the immunomodulatory role of TIM-3 in head and neck squamous cell carcinoma: implications for targeted therapy.Discover oncology · 2025Review
- Increased pathogenicity and pro-inflammatory capabilities of mucosal-associated invariant T cells involved in Oral Lichen Planus.BMC oral health · 2024Article
- Primary and acquired resistance to first-line therapy for clear cell renal cell carcinoma.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- The Double Game Played by Th17 Cells in Infection: Host Defense and Immunopathology.Pathogens (Basel, Switzerland) · 2022Review
- Deeper insight into the role of IL-17 in the relationship beween hypertension and intestinal physiology.Journal of inflammation (London, England) · 2022Review
- The tumor innate immune microenvironment in prostate cancer: an overview of soluble factors and cellular effectors.Exploration of targeted anti-tumor therapy · 2022Review
- Immune Checkpoints in Viral Infections.Viruses · 2020Review
- Immunomodulation of the Natural Killer Cell Phenotype and Response during HCV Infection.Journal of clinical medicine · 2020Review
- Intrahepatic TFrontiers in pharmacology · 2020Review
- Regulation of Monocyte-Macrophage Responses in Cirrhosis-Role of Innate Immune Programming and Checkpoint Receptors.Frontiers in immunology · 2019Review
- Mononuclear phagocyte system in hepatitis C virus infection.World journal of gastroenterology · 2018Review
- Interleukin (IL)-12 and IL-23 and Their Conflicting Roles in Cancer.Cold Spring Harbor perspectives in biology · 2018Review
- Polymorphisms in the Th17 cell-related RORC gene are associated with spontaneous clearance of HCV in Chinese women.BMC infectious diseases · 2018Article
- The proportion of different interleukin-17-producing T-cell subsets is associated with liver fibrosis in chronic hepatitis C.Immunology · 2017Article
- Tim-3 and its role in regulating anti-tumor immunity.Immunological reviews · 2017Review
- HCV-induced miR146a controls SOCS1/STAT3 and cytokine expression in monocytes to promote regulatory T-cell development.Journal of viral hepatitis · 2016Article
- Involvement of the Interleukin-23/Interleukin-17 Axis in Chronic Hepatitis C Virus Infection and Its Treatment Responses.International journal of molecular sciences · 2016Article
- Role of Tim-3 in hepatitis B virus infection: An overview.World journal of gastroenterology · 2016Review
- Hepatitis C virus-induced reduction in miR-181a impairs CD4(+) T-cell responses through overexpression of DUSP6.Hepatology (Baltimore, Md.) · 2015Article
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Authors and funding
10 authors.
Funding
Abstract
Cytokine production by innate immunity is critical for shaping the adaptive immunity through regulation of T cell differentiation. In this report, we studied T cell immunoglobulin mucin domain protein 3 (Tim-3) expression on monocytes and its regulatory effect on interleukin-12 (IL-12)/IL-23 production by CD14(+) monocytes, as well as IL-17 production by CD4(+) T cells in individuals with chronic hepatitis C virus (HCV) infection. We found that Tim-3 and IL-23p19 are highly expressed and that IL-12p35 is inhibited in human CD14(+) monocytes, while IL-17 expression is upregulated in CD4(+) T cells, in chronically HCV-infected individuals compared to healthy subjects. Interestingly, Tim-3 expression is closely associated with the differential regulation of IL-12/IL-23 expression in CD14(+) monocytes and correlated to IL-17 production by CD4(+) T cells. These Tim-3-associated IL-12/IL-23/IL-17 dysregulations in HCV-infected individuals are also recapitulated in vitro by incubating healthy monocytes or peripheral blood mononuclear cells with Huh-7 hepatoma cells transfected with HCV RNA. Importantly, blocking Tim-3 signaling on monocytes restores the balance of IL-12/IL-23 through the intracellular STAT3 signaling, which in turn reverses the upregulated IL-17 expression both ex vivo and in vitro. Our findings suggest that Tim-3-mediated differential regulation of IL-12/IL-23 drives T(H)17 cell development, a milieu favoring viral persistence and autoimmune phenomenon during HCV infection.
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