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Until now, the mechanisms of cell-cell interaction between hepatocytes and KCs involved in immune-mediated hepatitis remains unclear. Here we dissected the impact of activated mTORC1 on the cell-cell interaction of KCs and hepatocyte in immune-mediated hepatitis. In the liver from patients with AIH and mice administrated with Con-A, mTORC1 was activated in both KCs and hepatocytes. The activated mTORC1 signal in hepatocytes with Con-A challenge caused a markedly production of miR-329-3p. Upregulated miR-329-3p inhibited SGMS1 expression in KCs through paracrine, resulting in the death of KCs. Most of maintained KCs were p-S6 positive and distributed in hepatocyte mTORC1 negative area. The activation of mTORC1 enabled KCs expressed complement factor B (CFB) to enhance the complement alternative system, which produced more complement factors to aggravate liver injury. Our findings remonstrate a heterogeneous role of mTORC1 in specific cell type for maintaining tolerogenic liver environment, and will form the basis for the development of new interventions against immune-mediated hepatitis.<\/jats:p>","DOI":"10.1038\/s41419-022-05487-0","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T14:03:00Z","timestamp":1670594580000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mechanistic target of rapamycin complex 1 orchestrates the interplay between hepatocytes and Kupffer cells to determine the outcome of immune-mediated hepatitis"],"prefix":"10.1038","volume":"13","author":[{"given":"Xiaoli","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingmiao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengru","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7616-2469","authenticated-orcid":false,"given":"Chunsun","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"5487_CR1","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1038\/nri2858","volume":"10","author":"AW Thomson","year":"2010","unstructured":"Thomson AW, Knolle PA. 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Toxicol Lett. 2016;258:101\u20137.","journal-title":"Toxicol Lett"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-022-05487-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-022-05487-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-022-05487-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T15:04:20Z","timestamp":1670598260000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-022-05487-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,9]]},"references-count":54,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["5487"],"URL":"https:\/\/doi.org\/10.1038\/s41419-022-05487-0","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,9]]},"assertion":[{"value":"2 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All studies with human material were approved by the ethics committee of the 2nd Affiliated Hospital of Nanjing Medical University. The diagnosis of AIH was defined according to the guidelines of the European Association for the Study of Liver Disease guidelines. Controls were adjacent healthy tissue. For the animal studies, a protocol detailing experimental procedures following to the guidelines of the Institutional Animal Care was submitted to\u2014and approved by\u2014the animal studies committee at Nanjing Medical University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"1031"}}