{"doi":"10.3390/cells13090756","title":"Selective Targeting of α4β7/MAdCAM-1 Axis Suppresses Fibrosis Progression by Reducing Proinflammatory T Cell Recruitment to the Liver","abstract":"Integrin α4β7+ T cells perpetuate tissue injury in chronic inflammatory diseases, yet their role in hepatic fibrosis progression remains poorly understood. Here, we report increased accumulation of α4β7+ T cells in the liver of people with cirrhosis relative to disease controls. Similarly, hepatic fibrosis in the established mouse model of CCl4-induced liver fibrosis was associated with enrichment of intrahepatic α4β7+ CD4 and CD8 T cells. Monoclonal antibody (mAb)-mediated blockade of α4β7 or its ligand mucosal addressin cell adhesion molecule (MAdCAM)-1 attenuated hepatic inflammation and prevented fibrosis progression in CCl4-treated mice. Improvement in liver fibrosis was associated with a significant decrease in the infiltration of α4β7+ CD4 and CD8 T cells, suggesting that α4β7/MAdCAM-1 axis regulates both CD4 and CD8 T cell recruitment to the fibrotic liver, and α4β7+ T cells promote hepatic fibrosis progression. Analysis of hepatic α4β7+ and α4β7- CD4 T cells revealed that α4β7+ CD4 T cells were enriched for markers of activation and proliferation, demonstrating an effector phenotype. The findings suggest that α4β7+ T cells play a critical role in promoting hepatic fibrosis progression, and mAb-mediated blockade of α4β7 or MAdCAM-1 represents a promising therapeutic strategy for slowing hepatic fibrosis progression in chronic liver diseases.","journal":"Cells","year":2024,"id":440231,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":711979,"name":"Ravi Rai","orcid":"0000-0003-2550-3811","position":1,"is_corresponding":false},{"id":1252246,"name":"Pabitra Bikash Pal","orcid":null,"position":2,"is_corresponding":false},{"id":1252247,"name":"Daniel Rossmiller","orcid":null,"position":3,"is_corresponding":false},{"id":1165863,"name":"Sudrishti Chaudhary","orcid":null,"position":4,"is_corresponding":false},{"id":1180851,"name":"Anna Chiaro","orcid":null,"position":5,"is_corresponding":false},{"id":1180852,"name":"Shannon Seaman","orcid":null,"position":6,"is_corresponding":false},{"id":242167,"name":"Aatur D. Singhi","orcid":"0000-0003-3930-7096","position":7,"is_corresponding":false},{"id":279404,"name":"Silvia Liu","orcid":"0000-0002-1840-9520","position":8,"is_corresponding":false},{"id":277667,"name":"Satdarshan P. Monga","orcid":"0000-0002-8437-3378","position":9,"is_corresponding":false},{"id":297247,"name":"Smita S. Iyer","orcid":"0000-0002-8918-7005","position":10,"is_corresponding":false},{"id":276859,"name":"Reben Raeman","orcid":"0000-0002-3914-1797","position":11,"is_corresponding":false},{"id":1180575,"name":"Biki Gupta","orcid":"0000-0002-2315-1026","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:00:57.233748Z","pmid":"38727292","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}