Alcohol (Fayetteville, N.Y.)最新文献

{"title":"Intestinal epithelial- or hepatocyte-specific deletion of polymeric immunoglobulin receptor does not alter ethanol-induced liver disease in mice.","authors":"David Schöler, Maximilian Joseph Brol, Aenne Harberts, Marcos F Fondevila, Tomohiro Nakamura, Yanhan Wang, Wenchao Wei, Bernd Schnabl","doi":"10.1016/j.alcohol.2026.107463","DOIUrl":"https://doi.org/10.1016/j.alcohol.2026.107463","url":null,"abstract":"<p><strong>Background: </strong>Secretory immunoglobulin A (IgA) is the dominant mucosal antibody and is transported across epithelial cells by the polymeric immunoglobulin receptor (Pigr). Although chronic alcohol consumption disrupts intestinal barrier function and alters mucosal immunity, the contribution of Pigr-mediated IgA transport to alcohol-associated liver disease (ALD) remains unclear.</p><p><strong>Methods: </strong>Intestinal epithelial cell-specific (Pigr^ΔIEC) and hepatocyte-specific (Pigr^ΔHep) Pigr-deficient mice and littermate controls were subjected to the oral chronic-plus-binge Lieber-DeCarli ethanol feeding model (NIAAA model). Pigr^ΔHep mice were additionally evaluated in an oral chronic Lieber-DeCarli ethanol feeding model for 8 weeks. Fecal immunoglobulin concentrations, liver injury, steatosis, inflammatory gene expression, bacterial translocation, and ethanol metabolism-associated genes were assessed.</p><p><strong>Results: </strong>Intestinal deletion of Pigr numerically reduced fecal IgA concentrations following ethanol feeding, although this difference did not reach statistical significance, whereas fecal IgM concentrations remained unchanged. Ethanol-induced liver injury, steatosis and inflammation were comparable between Pigr^ΔIEC and Pigr^fl/fl littermate mice. In addition, markers of bacterial translocation, including systemic lipopolysaccharide levels and hepatic bacterial DNA, were similar in both genotypes following ethanol administration. Hepatocyte-specific Pigr deletion similarly did not affect ethanol-induced liver injury, steatosis, inflammatory responses, or bacterial translocation in two ethanol feeding models.</p><p><strong>Conclusions: </strong>These findings demonstrate that deletion of Pigr in either intestinal epithelial cells or hepatocytes alone is insufficient to alter ethanol-induced liver disease, indicating that loss of Pigr in either compartment alone is insufficient to disrupt mucosal immune homeostasis during chronic ethanol exposure.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":" ","pages":"107463"},"PeriodicalIF":2.9,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}