Academic Journal
Experimental Models of Autoimmune Hepatitis: Disease Fidelity and Translational Relevance.
| Τίτλος: | Experimental Models of Autoimmune Hepatitis: Disease Fidelity and Translational Relevance. |
|---|---|
| Συγγραφείς: | Buitrago-Molina LE; Department of Gastroenterology, Hepatology, Infectious Disease and Endocrinology, Hannover Medical School, Hannover, Germany., Hardtke-Wolenski M; Department of Gastroenterology, Hepatology, Infectious Disease and Endocrinology, Hannover Medical School, Hannover, Germany.; Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. |
| Πηγή: | Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2026 Aug; Vol. 46 (8), pp. e70797. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101160857 Publication Model: Print Cited Medium: Internet ISSN: 1478-3231 (Electronic) Linking ISSN: 14783223 NLM ISO Abbreviation: Liver Int Subsets: MEDLINE |
| Imprint Name(s): | Publication: Malden, MA : Wiley-Blackwell Original Publication: Oxford, UK : Blackwell Munksgaard, c2003- |
| Ιατρικοί όροι (MeSH): | Hepatitis, Autoimmune*/immunology , Hepatitis, Autoimmune*/genetics , Hepatitis, Autoimmune*/pathology , Disease Models, Animal*, Liver/immunology ; Liver/pathology ; Animals ; Humans ; Translational Research, Biomedical |
| Περίληψη: | Autoimmune hepatitis (AIH) remains difficult to study mechanistically in patients because disease initiation is rarely observed directly, the relevant autoantigens differ across subsets, and clinically meaningful outcomes such as chronic inflammation, fibrosis, relapse, and treatment response evolve over time. Animal models therefore remain indispensable. At the same time, the field has become increasingly heterogeneous. Acute immune-mediated hepatitis systems, especially concanavalin A (ConA), dominate the recent literature because they are rapid, inexpensive, and experimentally tractable. However, ConA-induced hepatitis is not an antigen-driven autoimmune response and is better interpreted as acute bystander immune-mediated liver injury than as a stand-alone model of chronic AIH. In contrast, antigen-driven adenoviral models based on cytochrome P450 2D6 (CYP2D6) or formiminotransferase cyclodeaminase (FTCD), as well as genetically predisposed or spontaneous tolerance-defect models, provide stronger insight into loss of hepatic tolerance, chronicity, fibrosis, and the interaction between antigenic context and host susceptibility. This review proposes a pragmatic framework for evaluating AIH models on the basis of face validity, construct validity, predictive validity, chronicity, host susceptibility, and mechanistic fitness for a specific biological question. Using that framework, we classify current models into acute surrogate models, immunization- and xenoantigen-based systems, adenoviral antigen-driven chronic models, spontaneous and genetically predisposed models, transgenic or neoantigen-driven tolerance models, and humanized or microbiota-sensitive hybrid systems. We then synthesize what these systems have taught the field about central and peripheral tolerance, MHC and non-MHC genetic susceptibility, sex- and age-related disease context, CD4+ and CD8+ T-cell biology, B-cell function, regulatory T-cell instability, impaired suppressive function, defective IL-2-dependent regulation, macrophage and innate lymphocyte participation, cell-death programmes, and gut-liver or liver-microbiome interactions. A central conclusion emerges: AIH models are complementary tools with markedly different levels of disease fidelity, and they should not be treated as interchangeable. Acute systems remain useful for effector-phase biology and first-pass intervention studies, but the strongest translational inferences for chronic AIH come from antigen-defined chronic models and selected tolerance-defect systems. Future progress will depend on better benchmarking across models, stronger alignment with human immune profiling and ex vivo validation platforms, and wider use of tolerance-restoring rather than purely anti-inflammatory therapeutic strategies. (© 2026 The Author(s). Liver International published by John Wiley & Sons Ltd.) |
| References: | U. Christen, “Animal Models of Autoimmune Hepatitis,” Biochimica et Biophysica Acta ‐ Molecular Basis of Disease 1865, no. 5 (2019): 970–981. M. Hardtke‐Wolenski, R. Taubert, and E. Jaeckel, “Animal Models for Autoimmune Liver Disease–What Is Relevant for Immune‐Mediated Liver Disease,” Digestive Diseases 30, no. Suppl 1 (2012): 2–10. M. Hardtke‐Wolenski and E. Jaeckel, “Mouse Models for Experimental Autoimmune Hepatitis: Limits and Chances,” Digestive Diseases 28, no. 1 (2010): 70–79. P. Lapierre, K. Beland, I. Djilali‐Saiah, and F. Alvarez, “Type 2 Autoimmune Hepatitis Murine Model: The Influence of Genetic Background in Disease Development,” Journal of Autoimmunity 26, no. 2 (2006): 82–89. P. Lapierre, K. Beland, C. Martin, F. Alvarez, Jr., and F. Alvarez, “Forkhead Box p3+ Regulatory T Cell Underlies Male Resistance to Experimental Type 2 Autoimmune Hepatitis,” Hepatology 51, no. 5 (2010): 1789–1798. M. Hardtke‐Wolenski, J. Dywicki, K. Fischer, et al., “The Influence of Genetic Predisposition and Autoimmune Hepatitis Inducing Antigens in Disease Development,” Journal of Autoimmunity 78 (2017): 39–45. D. Lubbering, M. Preti, L. Schlott, et al., “Autoantigen‐Selected B Cells Are Bystanders in Spontaneous T Cell‐Driven Experimental Autoimmune Hepatitis,” Immunology 170, no. 2 (2023): 214–229. D. Poddighe, T. Maulenkul, G. Zhubanova, L. Akhmaldtinova, and K. Dossybayeva, “Natural Killer T (NKT) Cells in Autoimmune Hepatitis: Current Evidence From Basic and Clinical Research,” Cells 12, no. 24 (2023): 2854. T. Nabekura, S. Matsuo, and A. Shibuya, “Concanavalin‐A‐Induced Acute Liver Injury in Mice,” Current Protocols 4, no. 8 (2024): e1117. M. Song, X. Gao, R. Kou, et al., “Sensitivity and Stability of Balb/c, C57BL/6J, and ICR Mice to the Acute Liver Injury Induced by Concanavalin A,” Toxicology Research 14, no. 2 (2025): tfaf036. T. Mori, Y. Mori, H. Yoshida, et al., “Cell‐Mediated Cytotoxicity of Sensitized Spleen Cells Against Target Liver Cells–In Vivo and In Vitro Study With a Mouse Model of Experimental Autoimmune Hepatitis,” Hepatology 5, no. 5 (1985): 770–777. M. Ogawa, Y. Mori, T. Mori, et al., “Adoptive Transfer of Experimental Autoimmune Hepatitis in Mice–Cellular Interaction Between Donor and Recipient Mice,” Clinical and Experimental Immunology 73, no. 2 (1988): 276–282. L. Zhu, D. Chen, Y. Zhu, et al., “GPX4‐Regulated Ferroptosis Mediates S100‐Induced Experimental Autoimmune Hepatitis Associated With the Nrf2/HO‐1 Signaling Pathway,” Oxidative Medicine and Cellular Longevity 2021 (2021): 6551069. Z. Y. Wang, P. P. Gao, L. Li, et al., “Dextran Sulfate Sodium‐Induced Gut Microbiota Dysbiosis Aggravates Liver Injury in Mice With S100‐Induced Autoimmune Hepatitis,” Immunology Letters 263 (2023): 70–77. P. Lapierre, I. Djilali‐Saiah, S. Vitozzi, and F. Alvarez, “A Murine Model of Type 2 Autoimmune Hepatitis: Xenoimmunization With Human Antigens,” Hepatology 39, no. 4 (2004): 1066–1074. P. Thomas‐Dupont, P. Grube‐Pagola, I. Y. Izaguirre‐Hernandez, et al., “Development of a New Murine Model of Type 2 Autoimmune Hepatitis Using a Human Liver Protein,” American Journal of Pathology 192, no. 1 (2022): 21–30. M. Holdener, E. Hintermann, M. Bayer, et al., “Breaking Tolerance to the Natural Human Liver Autoantigen Cytochrome P450 2D6 by Virus Infection,” Journal of Experimental Medicine 205, no. 6 (2008): 1409–1422. J. Ehser, M. Holdener, S. Christen, et al., “Molecular Mimicry Rather Than Identity Breaks T‐Cell Tolerance in the CYP2D6 Mouse Model for Human Autoimmune Hepatitis,” Journal of Autoimmunity 42 (2013): 39–49. E. Hintermann, J. Ehser, M. Bayer, J. M. Pfeilschifter, and U. Christen, “Mechanism of Autoimmune Hepatic Fibrogenesis Induced by an Adenovirus Encoding the Human Liver Autoantigen Cytochrome P450 2D6,” Journal of Autoimmunity 44 (2013): 49–60. P. Muller, M. Messmer, M. Bayer, J. M. Pfeilschifter, E. Hintermann, and U. Christen, “Non‐Alcoholic Fatty Liver Disease (NAFLD) Potentiates Autoimmune Hepatitis in the CYP2D6 Mouse Model,” Journal of Autoimmunity 69 (2016): 51–58. M. Hardtke‐Wolenski, K. Fischer, F. Noyan, et al., “Genetic Predisposition and Environmental Danger Signals Initiate Chronic Autoimmune Hepatitis Driven by CD4+ T Cells,” Hepatology 58, no. 2 (2013): 718–728. J. Dywicki, L. E. Buitrago‐Molina, J. Pietrek, et al., “Autoimmune Hepatitis Induction Can Occur in the Liver,” Liver International 40, no. 2 (2020): 377–381. M. Yuksel, Y. Wang, N. Tai, et al., “A Novel ‘Humanized Mouse’ Model for Autoimmune Hepatitis and the Association of Gut Microbiota With Liver Inflammation,” Hepatology 62, no. 5 (2015): 1536–1550. M. Yuksel, X. Xiao, N. Tai, et al., “The Induction of Autoimmune Hepatitis in the Human Leucocyte Antigen‐DR4 Non‐Obese Diabetic Mice Autoimmune Hepatitis Mouse Model,” Clinical and Experimental Immunology 186, no. 2 (2016): 164–176. A. J. Bonito, C. Aloman, M. I. Fiel, et al., “Medullary Thymic Epithelial Cell Depletion Leads to Autoimmune Hepatitis,” Journal of Clinical Investigation 123, no. 8 (2013): 3510–3524. M. Hardtke‐Wolenski, R. Taubert, F. Noyan, et al., “Autoimmune Hepatitis in a Murine Autoimmune Polyendocrine Syndrome Type 1 Model Is Directed Against Multiple Autoantigens,” Hepatology 61, no. 4 (2015): 1295–1305. J. Long, S. Y. Yang, M. X. Huang, et al., “Spontaneous Development of an Autoimmune Hepatitis ‐ Primary Biliary Cholangitis Overlap Syndrome in dnTGFbetaRII Aire(‐/‐) Mice,” Journal of Pathology 260, no. 2 (2023): 222–234. N. Aoki, M. Kido, S. Iwamoto, et al., “Dysregulated Generation of Follicular Helper T Cells in the Spleen Triggers Fatal Autoimmune Hepatitis in Mice,” Gastroenterology 140, no. 4 (2011): 1322–1333.e1–5. K. Yilmaz, S. Haeberle, Y. O. Kim, et al., “Regulatory T‐Cell Deficiency Leads to Features of Autoimmune Liver Disease Overlap Syndrome in Scurfy Mice,” Frontiers in Immunology 14 (2023): 1253649. K. Hao, K. M. Gao, M. Strauss, S. Subramanian, and A. Marshak‐Rothstein, “IFNgamma Initiates TLR9‐Dependent Autoimmune Hepatitis in DNase II Deficient Mice,” bioRxiv (2024). D. G. Bowen, A. Warren, T. Davis, et al., “Cytokine‐Dependent Bystander Hepatitis due to Intrahepatic Murine CD8 T‐Cell Activation by Bone Marrow‐Derived Cells,” Gastroenterology 123, no. 4 (2002): 1252–1264. K. Derkow, C. Loddenkemper, J. Mintern, et al., “Differential Priming of CD8 and CD4 T‐Cells in Animal Models of Autoimmune Hepatitis and Cholangitis,” Hepatology 46, no. 4 (2007): 1155–1165. J. Buxbaum, P. Qian, P. M. Allen, and M. G. Peters, “Hepatitis Resulting From Liver‐Specific Expression and Recognition of Self‐Antigen,” Journal of Autoimmunity 31, no. 3 (2008): 208–215. K. Beland, P. Lapierre, I. Djilali‐Saiah, and F. Alvarez, “Liver Restores Immune Homeostasis After Local Inflammation Despite the Presence of Autoreactive T Cells,” PLoS One 7, no. 10 (2012): e48192. S. Chabot, A. Fakhfakh, K. Beland, et al., “Mouse Liver‐Specific CD8(+) T‐Cells Encounter Their Cognate Antigen and Acquire Capacity to Destroy Target Hepatocytes,” Journal of Autoimmunity 42 (2013): 19–28. S. Manfredo Vieira, M. Hiltensperger, V. Kumar, et al., “Translocation of a Gut Pathobiont Drives Autoimmunity in Mice and Humans,” Science 359, no. 6380 (2018): 1156–1161. M. Liang, Z. Liwen, S. Jianguo, et al., “Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition,” Frontiers in Immunology 12 (2021): 728723. S. P. Pandey, M. J. Bender, A. C. McPherson, et al., “Tet2 Deficiency Drives Liver Microbiome Dysbiosis Triggering Tc1 Cell Autoimmune Hepatitis,” Cell Host & Microbe 30, no. 7 (2022): 1003–1019.e1010. L. Zhu, Y. Liang, L. Yang, et al., “Helicobacter mastomyrinus Infection Induces Autoimmune Hepatitis in Mice,” Journal of Translational Autoimmunity 10 (2025): 100275. M. Song, H. Wang, X. Tian, et al., “TIPE2 Protein Restrains Invariant NKT Activation and Protects Against Immune‐Mediated Hepatitis in Mice,” Hepatology 81, no. 6 (2025): 1671–1684. J. Sun, H. Xu, B. Li, et al., “IFITM1 Aggravates ConA‐Induced Autoimmune Hepatitis by Promoting NKT Cell Activation Through Increased AMPK‐Dependent Mitochondrial Function,” International Immunopharmacology 144 (2025): 113692. X. Wei, X. Cheng, Y. Luo, and X. Li, “Umbilical Cord‐Derived Mesenchymal Stem Cells Attenuate S100‐Induced Autoimmune Hepatitis via Modulating Th1 and Th17 Cell Responses in Mice,” Stem Cells International 2023 (2023): 9992207. H. Zhao, Y. Luo, Q. Li, X. Wei, and X. Li, “All‐Trans Retinoic Acid Ameliorates S100‐Induced Experimental Autoimmune Hepatitis by Regulating the Treg/Th17 Balance,” Immunopharmacology and Immunotoxicology 47, no. 5 (2025): 716–726. E. Hintermann, M. Holdener, M. Bayer, et al., “Epitope Spreading of the Anti‐CYP2D6 Antibody Response in Patients With Autoimmune Hepatitis and in the CYP2D6 Mouse Model,” Journal of Autoimmunity 37, no. 3 (2011): 242–253. L. E. Buitrago‐Molina, J. Dywicki, F. Noyan, et al., “Splenectomy Prior to Experimental Induction of Autoimmune Hepatitis Promotes More Severe Hepatic Inflammation, Production of IL‐17 and Apoptosis,” Biomedicine 9, no. 1 (2021): 58. J. Dywicki, L. E. Buitrago‐Molina, F. Noyan, et al., “Splenectomy Induces Biochemical Remission and Regeneration in Experimental Murine Autoimmune Hepatitis,” European Journal of Medical Research 27, no. 1 (2022): 284. A. Ikeda, N. Aoki, M. Kido, et al., “Progression of Autoimmune Hepatitis Is Mediated by IL‐18‐Producing Dendritic Cells and Hepatic CXCL9 Expression in Mice,” Hepatology 60, no. 1 (2014): 224–236. S. Iwamoto, M. Kido, N. Aoki, et al., “TNF‐Alpha Is Essential in the Induction of Fatal Autoimmune Hepatitis in Mice Through Upregulation of Hepatic CCL20 Expression,” Clinical Immunology 146, no. 1 (2013): 15–25. K. Alexandropoulos, A. J. Bonito, E. G. Weinstein, and O. Herbin, “Medullary Thymic Epithelial Cells and Central Tolerance in Autoimmune Hepatitis Development: Novel Perspective From a New Mouse Model,” International Journal of Molecular Sciences 16, no. 1 (2015): 1980–2000. N. Kruse, K. Neumann, A. Schrage, et al., “Priming of CD4+ T Cells by Liver Sinusoidal Endothelial Cells Induces CD25low Forkhead Box Protein 3‐ Regulatory T Cells Suppressing Autoimmune Hepatitis,” Hepatology 50, no. 6 (2009): 1904–1913. J. Dywicki, F. Noyan, A. C. Misslitz, et al., “Hepatic T Cell Tolerance Induction in an Inflammatory Environment,” Digestive Diseases 36, no. 2 (2018): 156–166. W. Shao, W. Huang, Y. Wang, et al., “Exosome‐Modified AAV Gene Therapy Attenuates Autoimmune Hepatitis via Enhanced Regulatory T Cell Targeting and Immune Modulation,” Microorganisms 13, no. 4 (2025): 823. Z. Zheng, Y. Liu, G. Wang, et al., “In Vivo CAR‐Tfh Cell Reprogramming Restores Tolerance in a Mouse Model of Autoimmune Hepatitis,” Cell Stem Cell 33 (2026): 589–604.e5. L. E. Buitrago‐Molina, J. Pietrek, F. Noyan, et al., “Treg‐Specific IL‐2 Therapy Can Reestablish Intrahepatic Immune Regulation in Autoimmune Hepatitis,” Journal of Autoimmunity 117 (2021): 102591. A. K. Horst, C. Wegscheid, C. Schaefers, et al., “Carcinoembryonic Antigen‐Related Cell Adhesion Molecule 1 Controls IL‐2‐Dependent Regulatory T‐Cell Induction in Immune‐Mediated Hepatitis in Mice,” Hepatology 68, no. 1 (2018): 200–214. H. Wang, S. Wang, Y. Lei, et al., “Serum Amyloid A1‐Induced Intrahepatic Regulatory T‐Cell Dysfunction Drives Autoimmune Hepatitis Progression,” Hepatology 83 (2025): 1049–1065. L. Zhang, B. Gromova, D. H. Nguyen, et al., “Inhibition of Estrogen Receptor Alpha Stabilizes Regulatory T Cell Function in Autoimmune Hepatitis,” JHEP Reports 8, no. 2 (2026): 101678. J. Zhao, F. Chu, H. Xu, et al., “C/EBPalpha/miR‐7 Controls CD4(+) T‐Cell Activation and Function and Orchestrates Experimental Autoimmune Hepatitis in Mice,” Hepatology 74, no. 1 (2021): 379–396. J. Long, S. Y. Yang, Z. H. Bian, et al., “PD‐1(+)CD8(+) T Cell‐Mediated Hepatocyte Pyroptosis Promotes Progression of Murine Autoimmune Liver Disease,” Advanced Science 12, no. 1 (2025): e2407284. Q. He, Y. Lu, W. Tian, et al., “TOX Deficiency Facilitates the Differentiation of IL‐17A‐Producing Gammadelta T Cells to Drive Autoimmune Hepatitis,” Cellular & Molecular Immunology 19, no. 10 (2022): 1102–1116. Z. Xiao, S. Wang, L. Luo, et al., “Lkb1 Orchestrates Gammadelta T‐Cell Metabolic and Functional Fitness to Control IL‐17‐Mediated Autoimmune Hepatitis,” Cellular & Molecular Immunology 21, no. 6 (2024): 546–560. K. Beland, G. Marceau, A. Labardy, S. Bourbonnais, and F. Alvarez, “Depletion of B Cells Induces Remission of Autoimmune Hepatitis in Mice Through Reduced Antigen Presentation and Help to T Cells,” Hepatology 62, no. 5 (2015): 1511–1523. L. E. Buitrago‐Molina, J. Dywicki, F. Noyan, et al., “Anti‐CD20 Therapy Alters the Protein Signature in Experimental Murine AIH, but Not Exclusively Towards Regeneration,” Cells 10, no. 6 (2021): 1471. S. Fujimori, P. S. Chu, T. Teratani, et al., “IL‐15‐Producing Splenic B Cells Play Pathogenic Roles in the Development of Autoimmune Hepatitis,” JHEP Reports 5, no. 7 (2023): 100757. N. Cui, Q. Qian, Y. Zhou, et al., “Extracellular Inosine Induces Anergy in B Cells to Alleviate Autoimmune Hepatitis,” Cellular and Molecular Gastroenterology and Hepatology 19, no. 10 (2025): 101539. B. Lin, H. Zhang, P. Zhu, et al., “Bone Marrow‐Derived CD169(+) Macrophages Promote Autoimmune Hepatitis by Recruiting CCR2(+) Monocytes via Secreting CCL12,” Experimental & Molecular Medicine 57, no. 12 (2025): 2930–2942. L. Zeng, Y. Wang, Y. Huang, et al., “IRG1/Itaconate Enhances Efferocytosis by Activating Nrf2‐TIM4 Signaling Pathway to Alleviate Con A Induced Autoimmune Liver Injury,” Cell Communication and Signaling: CCS 23, no. 1 (2025): 63. Z. Lyu, B. Huang, J. Zhang, et al., “Suppression of YTHDF2 Attenuates Autoimmune Hepatitis by Expansion of Myeloid‐Derived Suppressor Cells,” Journal of Autoimmunity 135 (2023): 102993. Y. Che, Y. Shi, Y. Xu, et al., “Gut Microbiota Dysbiosis and LPS/NLRP3/GSDMD Pyroptosis Drive Hepatic Fibrosis: Therapeutic Potential of a Synbiotic Intervention,” Probiotics and Antimicrobial Proteins 18 (2025): 4906–4924. Y. Chen, W. Li, S. Wang, et al., “A20‐Mediated KEAP1 Ubiquitination Orchestrates Hepatocyte Ferroptosis to Ameliorate Autoimmune Hepatitis,” Gut 75 (2025): 1573–1586. J. Lin, K. Feng, F. Wang, Z. Zheng, X. Luo, and C. Mo, “Nlrp12‐Driven PANoptosis Exacerbates Liver Injury in ConA‐Induced Autoimmune Hepatitis,” Genes and Immunity 27 (2026): 236–244. Y. Kang, X. Kuang, H. Yan, et al., “A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota‐Liver Axis and Inhibiting the Hepatic TLR4/NF‐kappaB/NLRP3 Signaling Pathway,” mSystems 8, no. 2 (2023): e0112722. B. Li, X. Liang, Y. Li, et al., “Tryptophan Catabolites From Microbiota Ameliorate Immune‐Mediated Hepatitis Through Activating Aryl Hydrocarbon Receptor of T Cells,” Gut Microbes 17, no. 1 (2025): 2557979. H. Yang, Q. Liu, H. Liu, et al., “Berberine Alleviates Concanavalin A‐Induced Autoimmune Hepatitis in Mice by Modulating the Gut Microbiota,” Hepatology Communications 8, no. 4 (2024): e0381. P. Lapierre, K. Beland, R. Yang, and F. Alvarez, “Adoptive Transfer of Ex Vivo Expanded Regulatory T Cells in an Autoimmune Hepatitis Murine Model Restores Peripheral Tolerance,” Hepatology 57, no. 1 (2013): 217–227. X. Bai, T. Chen, Y. Li, et al., “PD‐L1 Expression Levels in Mesenchymal Stromal Cells Predict Their Therapeutic Values for Autoimmune Hepatitis,” Stem Cell Res Ther 14, no. 1 (2023): 370. X. Bai, T. Liu, C. Li, et al., “PD‐L1 and ICAM1 Over Expression Empowers Immunoregulation of Mesenchymal Stromal Cells to Improve the Autoimmune Hepatitis Treatment Efficacy,” Stem Cell Res Ther 16, no. 1 (2025): 209. M. Shen, L. Zhou, X. Fan, et al., “Metabolic Reprogramming of CD4(+) T Cells by Mesenchymal Stem Cell‐Derived Extracellular Vesicles Attenuates Autoimmune Hepatitis Through Mitochondrial Protein Transfer,” International Journal of Nanomedicine 19 (2024): 9799–9819. F. Yang, B. Ni, X. Liang, et al., “Mesenchymal Stromal Cell‐Derived Extracellular Vesicles as Nanotherapeutics for Concanavalin a‐Induced Hepatitis: Modulating the Gut–Liver Axis,” Stem Cell Res Ther 16, no. 1 (2025): 4. J. Wu, S. Lyu, D. Guo, N. Yang, and Y. Liu, “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 15 (2024): 1488125. L. Gao, W. Zhang, L. Zhang, et al., “Silencing of Aryl Hydrocarbon Receptor Repressor Restrains Th17 Cell Immunity in Autoimmune Hepatitis,” Journal of Autoimmunity 143 (2024): 103162. C. Jin, B. B. Gao, W. J. Zhou, et al., “Hydroxychloroquine Attenuates Autoimmune Hepatitis by Suppressing the Interaction of GRK2 With PI3K in T Lymphocytes,” Frontiers in Pharmacology 13 (2022): 972397. X. Li, Y. Zhang, J. Wang, et al., “zVAD Alleviates Experimental Autoimmune Hepatitis in Mice by Increasing the Sensitivity of Macrophage to TNFR1‐Dependent Necroptosis,” Journal of Autoimmunity 133 (2022): 102904. Z. Liu, M. Sun, W. Liu, et al., “Deficiency of Purinergic P2X4 Receptor Alleviates Experimental Autoimmune Hepatitis in Mice,” Biochemical Pharmacology 221 (2024): 116033. J. Salimian, S. Vazifedust, M. Mirzaei Nodooshan, and H. Esmaeili Gouvarchinghaleh, “Natural Products in the Treatment of Autoimmune Hepatitis: A Comprehensive Review of Therapeutic Potential and Mechanisms,” International Immunopharmacology 164 (2025): 115366. A. Cardon, T. Guinebretiere, C. Dong, et al., “Single Cell Profiling of Circulating Autoreactive CD4 T Cells From Patients With Autoimmune Liver Diseases Suggests Tissue Imprinting,” Nature Communications 16, no. 1 (2025): 1161. M. Kramer, F. Mele, S. Jovic, et al., “Clonal Analysis of SepSecS‐Specific B and T Cells in Autoimmune Hepatitis,” Journal of Clinical Investigation 135, no. 2 (2025): e183776. C. Saggau, P. Bacher, D. Esser, et al., “Autoantigen‐Specific CD4(+) T Cells Acquire an Exhausted Phenotype and Persist in Human Antigen‐Specific Autoimmune Diseases,” Immunity 57, no. 10 (2024): 2416–2432.e2418. A. Klepper, J. Asaki, C. M. Caspar, et al., “Immune Profiling Links Autoimmune Hepatitis to Human Herpesvirus 6 and Relaxin Receptor Antigens,” Journal of Experimental Medicine 223, no. 4 (2026): e20250959. S. Nuciforo and M. H. Heim, “Organoids to Model Liver Disease,” JHEP Reports 3, no. 1 (2021): 100198. P. Olinga and D. Schuppan, “Precision‐Cut Liver Slices: A Tool to Model the Liver Ex Vivo,” Journal of Hepatology 58, no. 6 (2013): 1252–1253. |
| Contributed Indexing: | Keywords: CYP2D6; ConA; FTCD; Treg; animal models; autoimmune hepatitis; fibrosis; hepatic tolerance; murine model; translational immunology |
| Entry Date(s): | Date Created: 20260714 Date Completed: 20260714 Latest Revision: 20260726 |
| Update Code: | 20260726 |
| PubMed Central ID: | PMC13366445 |
| DOI: | 10.1111/liv.70797 |
| PMID: | 42444618 |
| Βάση Δεδομένων: | MEDLINE |
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