ArticleCellular and molecular gastroenterology and hepatology2021
MAdCAM-1/α4β7 Integrin-Mediated Lymphocyte/Endothelium Interactions Exacerbate Acute Immune-Mediated Hepatitis in Mice.
Article in Cellular and molecular gastroenterology and hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- The gut-lung axis and viral pneumonia: Unrevealing the gut microbiota.Pharmaceutical science advances · 2026Review
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Inflammatory gut-liver crosstalk: mechanisms and therapeutic targets.Experimental & molecular medicine · 2026Review
- The gut-liver axis in drug-induced liver injury (DILI): Interplay between gut microbiota, intestinal barrier, and immune system.Acta pharmaceutica Sinica. B · 2026Review
- Soluble mucosal addressin cell adhesion molecule 1 is a biomarker for pediatric ulcerative colitis.Molecular and cellular pediatrics · 2026Article
- Lymphocyte homing disorder: a concealed driver of intestinal immune collapse in sepsis.Frontiers in immunology · 2026Review
- Integrin α4β7: Pathogenic Roles in Metabolic and Inflammatory Diseases and Translational Therapeutics.Journal of inflammation research · 2026Review
- Revealing the pathogenesis of autoimmune hepatitis and research progress in drug discovery from hepatic immune cells and intercellular communication signaling mechanisms.Frontiers in immunology · 2026Review
- The Role and Application of MAdCAM-1/α4β7-Induced Lymphocyte Migration in Inflammatory Enterohepatic Diseases.Biomedicines · 2025Review
- Selective Targeting of αCells · 2024Article
- Role of intestinal flora in primary sclerosing cholangitis and its potential therapeutic value.World journal of gastroenterology · 2022Review
- Aberrant hepatic trafficking of gut-derived T cells is not specific to primary sclerosing cholangitis.Hepatology (Baltimore, Md.) · 2022Article
- Celastrol Alleviates Autoimmune Hepatitis Through the PI3K/AKT Signaling Pathway Based on Network Pharmacology and Experiments.Frontiers in pharmacology · 2022Article
- Targeting T Cell Subtypes for NAFLD and NAFLD-Related HCC Treatment: An Opinion.Frontiers in medicine · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsAberrant lymphocyte homing could potentially link inflammatory processes in the intestine and the liver, as distinct hepatobiliary diseases frequently develop as extra-intestinal manifestations in inflammatory bowel disease. In this study, we examined the role of the gut-tropic leukocyte adhesion molecule β7 integrin and its endothelial ligand mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) in immune-mediated hepatitis in mice.
methodsWild-type (WT) mice, MAdCAM-1-deficient mice, β7 integrin-deficient mice, RAG-2-deficient mice, RAG-2/MAdCAM-1 double-deficient mice, and RAG-2/β7 integrin double-deficient mice were subjected to concanavalin A (ConA)-induced hepatitis. The degree of hepatitis was evaluated by histology, flow cytometry, and expression analysis of inflammatory mediators. The motility of lymphocytes in progressive liver damage was assessed by intravital laser scanning multiphoton microscopy.
resultsAblation of MAdCAM-1 or β7 integrin ameliorated ConA-induced hepatitis in mice. β7 integrin-deficient lymphocytes caused less liver damage than WT lymphocytes in ConA-treated RAG-2-deficient mice. Moreover, WT lymphocytes caused less liver damage in ConA-treated RAG-2/β7 integrin double-deficient mice than in similarly treated RAG-2-deficient mice, indicating that β7 integrin expression contributes significantly to the liver damage mediated by innate immune cells. MAdCAM-1 expression was dependent on β7 integrin expression on adaptive and innate immune cells. Most importantly, lymphocytes in ConA-treated MAdCAM-1-deficient mice displayed more motility and less adhesion in the liver sinusoids in vivo, than lymphocytes in similarly treated WT mice.
conclusionsThese data suggest that β7 integrin expression on lymphocytes and innate immune cells contributes to MAdCAM-1 upregulation and liver damage in acute immune-mediated hepatitis, most likely by facilitating lymphocyte/sinusoidal endothelial cell interactions.
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