{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T05:16:15Z","timestamp":1788066975113,"version":"build-2784847793"},"reference-count":49,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2019YFA0802400"],"award-info":[{"award-number":["2019YFA0802400"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31571489"],"award-info":[{"award-number":["31571489"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["31571489"],"award-info":[{"award-number":["31571489"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatic inflammation is a defining feature of Metabolic Dysfunction-Associated Steatohepatitis (MASH), yet the specific contributions of individual immune cell populations and their reciprocal interactions remain incompletely understood. In this study, we combined flow cytometry with single-cell transcriptomic profiling to characterize the hepatic immune landscape in a novel model of spontaneous MASH caused by hepatocyte-specific deficiency of endoplasmic reticulum-associated degradation (ERAD). Hepatic ERAD deficiency led to the expansion of multiple immune cell populations in the liver, including CD8+ T cells, macrophages, monocytes, and dendritic cells, accompanied by extensive functional reprogramming of both innate and adaptive immune compartments. Myeloid cells exhibited enhanced phagocytic activity and increased antigen processing and presentation, whereas CD8+ T cells displayed elevated proliferation capacity, DNA repair activity and cytotoxicity. Notably, two functionally distinct triggering receptor expressed on myeloid cells 2 (TREM2)-expressing macrophage subsets emerged during the progression of ERAD deficiency-induced MASH. Depletion of CD8+ T cells increased monocyte infiltration and aggravated liver injury, suggesting that CD8+ T cells exert a previously unrecognized protective role by restraining monocyte recruitment. Collectively, these findings reveal highly coordinated interactions between innate and adaptive cells during MASH progression and identify CD8+ T cells as potential regulators of monocyte infiltration and hepatic injury.<\/jats:p>","DOI":"10.3390\/cells15171562","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:33:52Z","timestamp":1787942032000},"page":"1562","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatocyte-Specific Deficiency of Endoplasmic Reticulum-Associated Degradation Induces Coordinated Innate\u2013Adaptive Immune Responses"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2881-8969","authenticated-orcid":false,"given":"Qingqing","family":"Liu","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cam-Su Mouse Genomic Resources Center, Medical College, Soochow University, 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