{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T19:53:57Z","timestamp":1786823637498,"version":"build-2736575974"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The pathogenesis of biliary atresia (BA) is unclear to date and no therapies targeting immune regulatory pathways exist. Here we characterized potent effector liver tissue resident memory CD8<jats:sup>+<\/jats:sup> T cells (Trm) and monocytic cells in children with advanced BA and an age-matched control group to gain insight into BA pathogenesis and immunologic regulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Liver explants from 18 children with biliary atresia and 10 with metabolic disease and normal histology were analyzed <jats:italic>ex vivo<\/jats:italic> by multicolor flow-cytometry and immunohistochemistry. Cytokines and cytotoxic mediators were quantified by intracellular staining and bead-based arrays in culture supernatant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The frequency of CD103<jats:sup>+<\/jats:sup>CD69<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> Trm cells and CD14<jats:sup>+<\/jats:sup>CD16<jats:sup>+<\/jats:sup> monocytes was significantly higher in BA than in the control group. In BA, T cells showed elevated expression of CD103, CD69, CD39 and production of TNF-\u03b1 and Granzyme-B <jats:italic>ex vivo<\/jats:italic>, which could be reproduced <jats:italic>in vitro<\/jats:italic> by allowing cell-contact with monocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cytotoxic CD8<jats:sup>+<\/jats:sup> Trm cells and intrahepatic monocytes might contribute to tissue destruction in BA. Therapies targeting Trm cells or the TNF-\u03b1 signaling pathway could be explored to delay progression to cirrhosis in BA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1567645","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T05:46:51Z","timestamp":1750225611000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Expansion of CD103+CD69+CD8+ cytotoxic liver tissue resident memory T cells and inflammatory monocytes in advanced biliary atresia"],"prefix":"10.3389","volume":"16","author":[{"given":"Freya","family":"Sibbertsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regine J.","family":"Dress","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f6ren 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