ArticleThe American journal of pathology2014
STAT4 knockout mice are more susceptible to concanavalin A-induced T-cell hepatitis.
Article in The American journal of pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Demonstrating the immunostimulatory and cytokine-augmentation effects of bacterial ghosts on natural killer cells and Caenorhabditis Elegans.Biotechnology and bioengineering · 2024Article
- Natural Killer T (NKT) Cells in Autoimmune Hepatitis: Current Evidence from Basic and Clinical Research.Cells · 2023Review
- Concanavalin A as a promising lectin-based anti-cancer agent: the molecular mechanisms and therapeutic potential.Cell communication and signaling : CCS · 2022Review
- Microcirculatory disturbance in acute liver injury.Experimental and therapeutic medicine · 2021Article
- Genetic variants in STAT4 and their interactions with environmental factors for the incidence of hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2021Article
- Tyrosine kinase inhibitor neratinib attenuates liver fibrosis by targeting activated hepatic stellate cells.Scientific reports · 2020Article
- Manipulation of JAK/STAT Signalling by High-Risk HPVs: Potential Therapeutic Targets for HPV-Associated Malignancies.Viruses · 2020Review
- Comparative Assessment of the New PDE7 Inhibitor - GRMS-55 and Lisofylline in Animal Models of Immune-Related Disorders: A PK/PD Modeling Approach.Pharmaceutical research · 2020Article
- Kupffer cells promote T-cell hepatitis by producing CXCL10 and limiting liver sinusoidal endothelial cell permeability.Theranostics · 2020Article
- STAT4: an immunoregulator contributing to diverse human diseases.International journal of biological sciences · 2020Review
- RIPK3-Mediated Necroptosis and Neutrophil Infiltration Are Associated with Poor Prognosis in Patients with Alcoholic Cirrhosis.Journal of immunology research · 2018Article
- Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance.Hepatobiliary & pancreatic diseases international : HBPD INT · 2017Review
- Decreased STAT4 indicates poor prognosis and enhanced cell proliferation in hepatocellular carcinoma.World journal of gastroenterology · 2015Article
- Signal transducer and activator of transcription 4 in liver diseases.International journal of biological sciences · 2015Review
- Protective effect of galangin in Concanavalin A-induced hepatitis in mice.Drug design, development and therapy · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
STAT4, which is activated mainly by IL-12, promotes inflammatory responses by inducing Th1 and Th2 cytokines. Recent genome-wide association studies indicate that STAT4 gene variants are associated with risk of various types of liver diseases, but how STAT4 contributes to liver disease pathogenesis remains obscure. In this study, STAT4 activation was detected in liver immune cells from patients with viral hepatitis and autoimmune hepatitis, as well as in a mouse model of concanavalin A (Con A)-induced hepatitis. Such STAT4 activation was detected mainly in T cells, natural killer T cells, and macrophages and Kupffer cells, and was diminished in Il12a(-/-) and Il12b(-/-) mice. As expected, disruption of the Stat4 gene reduced production of Th1 and Th2 cytokines, but surprisingly exacerbated Con A-induced liver injury. Similarly, disruption of Il12a or Il12b also augmented Con A-induced hepatocellular damage. Further studies showed that hepatic natural killer T (NKT) cells from Con A-treated Stat4(-/-) mice had higher levels of FasL expression and increased cytotoxicity against hepatocytes than those from Con A-treated WT mice. In vitro, blocking FasL attenuated Stat4(-/-) NKT cytotoxicity against hepatocytes. In conclusion, despite up-regulation of proinflammatory cytokines, STAT4 protects against acute T-cell hepatitis, which is mediated by direct or indirect down-regulation of FasL expression on NKT cells.
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