ArticleHepatology (Baltimore, Md.)2015
A novel "humanized mouse" model for autoimmune hepatitis and the association of gut microbiota with liver inflammation.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 119 citations in OpenAlex.
- Immunomodulatory effects of tacrolimus-loaded lipid-core nanocapsules in autoimmune hepatitis.Journal of autoimmunity · 2026Article
- Experimental Models of Autoimmune Hepatitis: Disease Fidelity and Translational Relevance.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Gut Microbiota and Autoimmune Diseases: The Therapeutic Potential of Probiotics.Current microbiology · 2026Review
- The role of Traditional Chinese Medicine in the management of liver disease: targeting gut microbiome.Chinese medicine · 2026Review
- Regulatory T-cells in autoimmune hepatitis: An historical perspective with hints to the future.JHEP reports : innovation in hepatology · 2026Article
- Microbial Modulation of the Gut-Liver Axis in Autoimmune Liver Diseases.Seminars in liver disease · 2025Review
- The detrimental effect of autoimmune hepatitis in pregnancy: a systematic review and meta-analysis.Annals of medicine and surgery (2012) · 2025Article
- Dual regulatory role of natural killer T cells during development of hepatocellular carcinoma.Communications biology · 2025Article
- Gut microbial signatures in autoimmune hepatitis: unlocking diagnostic and therapeutic potential.Annals of medicine and surgery (2012) · 2025Article
- Effects of Probiotics on Liver Diseases: Current In Vitro and In Vivo Studies.Probiotics and antimicrobial proteins · 2025Review
- HLA alleles predisposing to autoimmunity are linked to impaired immunoregulation in patients with juvenile autoimmune liver disease and in their first-degree relatives.Journal of autoimmunity · 2025Article
- Harnessing the Power of Probiotics: Boosting Immunity and Safeguarding against Various Diseases and Infections.Recent advances in anti-infective drug discovery · 2025Review
- Association between ABO blood group system and autoimmune liver disease.Frontiers in medicine · 2025Article
- Interacting roles of gut microbiota and T cells in the development of autoimmune hepatitis.Frontiers in immunology · 2025Review
- Article
- Are Gender Differences Important for Autoimmune Liver Diseases?Life (Basel, Switzerland) · 2024Review
- Protective effects of YCHD on the autoimmune hepatitis mice model induced by Ad-CYP2D6 through modulating the Th1/Treg ratio and intestinal flora.Frontiers in immunology · 2024Article
- The significance of gut microbiota in the etiology of autoimmune hepatitis: a narrative review.Frontiers in cellular and infection microbiology · 2024Review
- Natural Killer T (NKT) Cells in Autoimmune Hepatitis: Current Evidence from Basic and Clinical Research.Cells · 2023Review
- Fecal microbiota transplantation regulates TFH/TFR cell imbalance via TLR/MyD88 pathway in experimental autoimmune hepatitis.Heliyon · 2023Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 8 institutions in 5 countries.
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Abstract
unlabelledAutoimmune hepatitis (AIH) in humans is a severe inflammatory liver disease characterized by interface hepatitis, the presence of circulating autoantibodies, and hyper-gammaglobulinemia. There are two types of AIH, type 1 (AIH-1) and type 2 (AIH-2), characterized by distinct autoimmune serology. Patients with AIH-1 are positive for anti-smooth muscle and/or antinuclear autoantibodies, whereas patients with AIH-2 have anti-liver kidney microsomal type 1 and/or anti-liver cytosol type 1 autoantibodies. Cytochrome P4502D6 is the antigenic target of anti-liver kidney microsomal type 1, and formiminotransferase cyclodeaminase is the antigenic target of anti-liver cytosol type 1. It is known that AIH, both types 1 and 2, is strongly linked to the human leukocyte antigen (HLA) alleles -DR3, -DR4, and -DR7. However, direct evidence of the association of HLA with AIH is lacking. We developed a novel mouse model of AIH using the HLA-DR3 transgenic mouse on the nonobese-diabetic background by immunization of HLA-DR3- and HLA-DR3+ nonobese-diabetic mice with a DNA plasmid, coding for human cytochrome P4502D6/formiminotransferase cyclodeaminase fusion protein. Immunization with cytochrome P4502D6/formiminotransferase cyclodeaminase leads to a sustained elevation of alanine aminotransferase, development of antinuclear autoantibodies and anti-liver kidney microsomal type 1/anti-liver cytosol type 1 autoantibodies, chronic immune cell infiltration, and parenchymal fibrosis on liver histology in HLA-DR3+ mice. Immunized mice also showed an enhanced T helper 1 immune response and paucity of the frequency of regulatory T cells in the liver. Moreover, HLA-DR3+ mice with exacerbated AIH showed reduced diversity and total load of gut bacteria.
conclusionOur humanized animal model has provided a novel experimental tool to further elucidate the pathogenesis of AIH and to evaluate the efficacy and safety of immunoregulatory therapeutic interventions in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.