{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:02:16Z","timestamp":1788350536870,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,13]],"date-time":"2022-11-13T00:00:00Z","timestamp":1668297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"the National Research Foundation (NRF) of Korea grant funded by the Korean government (MSIT)","doi-asserted-by":"publisher","award":["NRF-2020R1A2C3006952"],"award-info":[{"award-number":["NRF-2020R1A2C3006952"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fulminant hepatitis is characterized by rapid and massive immune-mediated liver injury. Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1; NR0B1) represses the transcription of various genes. Here, we determine whether DAX1 serves as a regulator of inflammatory liver injury induced by concanavalin A (ConA). C57BL\/6J (WT), myeloid cell-specific Dax1 knockout (MKO), and hepatocyte-specific Dax1 knockout (LKO) mice received single intravenous administration of ConA. Histopathological changes in liver and plasma alanine aminotransferase and aspartate aminotransferase levels in Dax1 MKO mice were comparable with those in WT mice following ConA administration. Unlike Dax1 MKO mice, Dax1 LKO mice were greatly susceptible to ConA-induced liver injury, which was accompanied by enhanced infiltration of immune cells, particularly CD4+ and CD8+ T cells, in the liver. Factors related to T-cell recruitment, including chemokines and adhesion molecules, significantly increased following enhanced and prolonged phosphorylation of NF-\u03baB p65 in the liver of ConA-administered Dax1 LKO mice. This is the first study to demonstrate that hepatocyte-specific DAX1 deficiency exacerbates inflammatory liver injury via NF-\u03baB p65 activation, thereby causing T-cell infiltration by modulating inflammatory chemokines and adhesion molecules. Our results suggest DAX1 as a therapeutic target for fulminant hepatitis treatment.<\/jats:p>","DOI":"10.3390\/ijms232214009","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T02:29:32Z","timestamp":1668392972000},"page":"14009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hepatocyte DAX1 Deletion Exacerbates Inflammatory Liver Injury by Inducing the Recruitment of CD4+ and CD8+ T Cells through NF-\u03baB p65 Signaling Pathway in Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Hyo-Jeong","family":"Yun","sequence":"first","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon 34113, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Joo","family":"Suh","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Bin","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Jung","family":"Kang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Hyeon","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Keun","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Bok","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Jeong","family":"Seo","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Ran","family":"Noh","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hueng-Sik","family":"Choi","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0682-2238","authenticated-orcid":false,"given":"Yong-Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon 34113, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6996-5746","authenticated-orcid":false,"given":"Chul-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon 34113, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"viii5","DOI":"10.1093\/ndt\/gfm650","article-title":"Fulminant hepatic failure: Etiology and indications for liver transplantation","volume":"22","author":"Gotthardt","year":"2007","journal-title":"Nephrol. 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