{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T19:59:44Z","timestamp":1762459184516,"version":"3.40.3"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2002,12,1]],"date-time":"2002-12-01T00:00:00Z","timestamp":1038700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Viral hepatitis affects more than 2 billion people worldwide. In particular, no effective treatment exists to abrogate death and liver damage in fulminant hepatitis. Activation of T cells is an initial and critical event in the pathogenesis of liver damage in autoimmune and viral hepatitis. The precise molecular mechanisms that induce T cell-mediated hepatocyte injury remain largely unclear. In mice, T cell-dependent hepatitis and acute liver damage can be modeled using ConA. In this study, we examined the role of the adhesion receptor LFA-1 in ConA-induced acute hepatic damage using LFA-1\u2212\/\u2212 (CD11a) mice. Massive liver cell apoptosis and metabolic liver damage were observed in LFA-1+\/+ mice following ConA injection. By contrast, LFA-1\u2212\/\u2212 mice were completely resistant to ConA-induced hepatitis and none of the LFA-1\u2212\/\u2212 mice showed any hepatic damage. Whereas activated hepatic T cells remained in the liver in LFA-1+\/+ mice, activated T cells were rapidly cleared from the livers of LFA-1\u2212\/\u2212 mice. Mechanistically, T cells from LFA-1\u2212\/\u2212 mice showed markedly reduced cytotoxicity toward liver cells as a result of impaired, activation-dependent adhesion. Importantly, adoptive transfer of hepatic T cells from LFA-1+\/+ mice, but not from LFA-1\u2212\/\u2212 mice, sensitized LFA-1\u2212\/\u2212 mice to ConA-induced hepatitis. Thus, LFA-1 expression on T cells is necessary and sufficient for T cell-mediated liver damage in vivo. These results provide the first genetic evidence on an adhesion receptor, LFA-1, that has a crucial role in fulminant hepatitis. These genetic data identify LFA-1 as a potential key target for the treatment of T cell-mediated hepatitis and the prevention of liver damage.<\/jats:p>","DOI":"10.4049\/jimmunol.169.12.7087","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T00:33:07Z","timestamp":1398040387000},"page":"7087-7096","source":"Crossref","is-referenced-by-count":24,"title":["Essential Role of the Adhesion Receptor LFA-1 for T Cell-Dependent Fulminant Hepatitis"],"prefix":"10.1093","volume":"169","author":[{"given":"Goichi","family":"Matsumoto","sequence":"first","affiliation":[{"name":"First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College , Kanagawa ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Tsunematsu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kitasato Institute Hospital , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei-ichi","family":"Tsukinoki","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Kanagawa Dental College , Kanagawa ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Ohmi","sequence":"additional","affiliation":[{"name":"First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College , Kanagawa ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariko","family":"Iwamiya","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Kanagawa Dental College , Kanagawa ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Oliveira-dos-Santos","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biotechnology of the Austrian Academy of Sciences and Department of Medical Biophysics and Immunology, Ontario Cancer Institute, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Tone","sequence":"additional","affiliation":[{"name":"First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College , Kanagawa ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junichi","family":"Shindo","sequence":"additional","affiliation":[{"name":"First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College , Kanagawa ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef M","family":"Penninger","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biotechnology of the Austrian Academy of Sciences and Department of Medical Biophysics and Immunology, Ontario Cancer Institute, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,12,15]]},"reference":[{"first-page":"189","volume-title":"Cytokine Growth Factor Rev.","year":"2001","key":"2025032711493987500_R1"},{"first-page":"431","volume-title":"Clin. 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