ArticleAlimentary pharmacology & therapeutics2022
Duodenal CD8+ T resident memory cell apoptosis contributes to gut barrier dysfunction and microbial translocation in early alcohol-associated liver disease in humans.
Article in Alimentary pharmacology & therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Influence of Alcohol on the Intestinal Immune System.Alcohol research : current reviews · 2025Pooled it
- Microbial cues and T cell immunity: deciphering their interactions in chronic liver disease.Experimental & molecular medicine · 2026Review
- Bidirectional interplay between gut and liver in inflammatory bowel disease and hepatobiliary conditions.Clinical and experimental medicine · 2026Review
- Parallel regulation of goblet cell-associated antigen passages by reduced microbial sensing and mAChR4 signaling in Muc2 deficiency prevents ethanol-induced liver injury.Hepatology (Baltimore, Md.) · 2026Article
- Intestinal neutral ceramidase exacerbates MASH pathogenesis.eGastroenterology · 2026Article
- Illustration of the gut-immune-liver axis in early-stage alcohol-related liver disease: role and non-invasive potentiation of biomarkers and peptidomic signatures.Npj gut and liver · 2026Article
- Review
- Article
- Article
- Article
- Metabolic dysfunction and alcohol-associated liver disease (MetALD).eGastroenterology · 2025Review
- Gut-liver axis: Recent concepts in pathophysiology in alcohol-associated liver disease.Hepatology (Baltimore, Md.) · 2024Review
- Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.Clinical and molecular hepatology · 2024Review
- The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease.Nature reviews. Gastroenterology & hepatology · 2023Review
- Tissue-resident and innate-like T cells in patients with advanced chronic liver disease.JHEP reports : innovation in hepatology · 2023Review
- Alcohol-associated bowel disease: new insights into pathogenesis.eGastroenterology · 2023Article
- Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways.Cell death & disease · 2023Review
- Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundIntestinal T cells are key in gut barrier function. Their role in early stages of alcohol-associated liver disease (ALD) remain unknown.
aimTo explore the links between intestinal T cells, microbial translocation and ALD
methodsPatients 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.
resultsPatients 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.
conclusionsDuodenal 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.
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