{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:23:32Z","timestamp":1790223812161,"version":"4.1.0"},"reference-count":146,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The gut and liver form an anatomical and functional unit linked by the portal circulation, the biliary tract, lymphatic drainage, and neuroimmune pathways. In recent years, the classical gut-liver axis has expanded from a predominantly microbial and metabolic concept into a broader framework in which immune cells are viewed as central integrators of inter-organ signaling. In health, balanced microbial sensing, intact mucosal and vascular barriers, regulated bile acid signaling, and specialized tissue-resident immune programs preserve tolerance at both intestinal and hepatic interfaces. In disease, dysbiosis, barrier failure, altered bile acid pools, endogenous hepatotoxic metabolites, and aberrant immune-cell trafficking remodel the hepatic immune niche and drive steatohepatitis, alcohol-associated liver injury, cholangiopathy, cirrhosis, acute decompensation, and hepatocellular carcinoma. This review reframes the gut-liver axis as a gut-liver-immune axis and synthesizes current evidence on its structural basis, cellular architecture, molecular mediators, and disease-specific manifestations. We discuss the roles of macrophages, dendritic cells, neutrophils, innate-like T cells, natural killer cells, and adaptive T-cell subsets in translating gut-derived signals into hepatic inflammation, tissue repair, fibrosis, or tumor surveillance. We also highlight the bidirectional role of the liver in shaping intestinal immunity, particularly through bile acids and hepatobiliary-derived mediators. Finally, we examine current therapeutic strategies targeting the microbiota, mucosal barrier, bile acid signaling, and immune-cell trafficking, and we outline major conceptual and translational gaps that should guide the next generation of mechanistic and clinical studies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1864805","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T08:54:04Z","timestamp":1785747244000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The gut-liver-immune axis: structural basis, cellular architecture, molecular mediators, and disease-specific manifestations"],"prefix":"10.3389","volume":"17","author":[{"given":"Sang Jun","family":"Yoon","sequence":"first","affiliation":[{"name":"Institute for Liver and Digestive Diseases, Hallym University College of Medicine","place":["Chuncheon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung A","family":"Eom","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, Hallym University College of Medicine","place":["Chuncheon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Tae","family":"Suk","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, Hallym University College of Medicine","place":["Chuncheon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/liv.13682","article-title":"Liver diseases: a major, neglected global public health problem requiring urgent actions and large-scale screening","volume":"38","author":"Marcellin","year":"2018","journal-title":"Liver 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