{"doi":"10.1111/apt.17177","title":"Duodenal <scp>CD8</scp>+ T resident memory cell apoptosis contributes to gut barrier dysfunction and microbial translocation in early alcohol‐associated liver disease in humans","abstract":"BACKGROUND: Intestinal T cells are key in gut barrier function. Their role in early stages of alcohol-associated liver disease (ALD) remain unknown. AIM: To explore the links between intestinal T cells, microbial translocation and ALD METHODS: Patients with alcohol use disorder (AUD) following a rehabilitation programme were compared to subjects with non-alcoholic fatty liver disease (NAFLD) and healthy controls. Clinical and laboratory data (liver stiffness, controlled attenuation parameter, AST, ALT, K18-M65) served to identify AUD patients with isolated steatosis (minimal liver disease) or steatohepatitis/fibrosis (ALD). Serum microbial translocation markers were measured by ELISA, duodenal and plasma levels of sphingolipids by targeted LC-MS. T lymphocytes in duodenal biopsies were characterised by immunohistochemistry, flow cytometry and RNA sequencing on FACS-sorted cells. Mechanisms for T-cell alterations were assessed in vitro. RESULTS: Patients with ALD, but not those with minimal liver disease, showed reduced numbers of duodenal CD8+ T resident memory (TRM) cells compared to controls or patients with NAFLD. TRM transcriptomic analysis, in vitro analyses and pharmacological inhibition of cathepsin B confirmed TRM apoptosis driven by lysosomal membrane permeabilisation and cathepsin B release into the cytosol. Altered lipid metabolism and increased duodenal and plasma sphingolipids correlated with apoptosis. Dihydroceramide dose-dependently reduced viability of TRM. Duodenal TRM phenotypic changes, apoptosis and transcriptomic alterations correlated with increased levels of microbial translocation markers. Short-term abstinence did not reverse TRM cell death in patients with ALD. CONCLUSIONS: Duodenal CD8+ TRM apoptosis related to functional changes in lysosomes and lipid metabolism points to impaired gut adaptive immunity specifically in patients with AUD who developed early ALD.","journal":"Alimentary Pharmacology & Therapeutics","year":2022,"id":253663,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":899635,"name":"Axelle Loriot","orcid":"0000-0002-5288-8561","position":1,"is_corresponding":false},{"id":899636,"name":"Joseph P. Dewulf","orcid":"0000-0001-7223-2706","position":2,"is_corresponding":false},{"id":675814,"name":"Guido T. Bommer","orcid":"0000-0001-6898-4884","position":3,"is_corresponding":false},{"id":254373,"name":"Yves Horsmans","orcid":"0000-0002-5779-2454","position":4,"is_corresponding":false},{"id":899637,"name":"Nicolas Lanthier","orcid":"0000-0002-7651-9314","position":5,"is_corresponding":false},{"id":254375,"name":"Isabelle Leclercq","orcid":"0000-0001-7934-6693","position":6,"is_corresponding":false},{"id":239670,"name":"Bernd Schnabl","orcid":"0000-0002-6281-825X","position":7,"is_corresponding":false},{"id":245705,"name":"Peter Stärkel","orcid":"0000-0003-2938-4442","position":8,"is_corresponding":false},{"id":254371,"name":"Luca Maccioni","orcid":"0000-0003-3727-0664","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T00:24:59.596040Z","pmid":"35919965","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":[]}