{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T18:07:01Z","timestamp":1776276421986,"version":"3.50.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T00:00:00Z","timestamp":1259625600000},"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":[[2009,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Suppressor of cytokine signaling 3 (SOCS3), a negative-feedback molecule for cytokine signaling, has been implicated in protection against liver injury. Previous studies have shown that overexpression of SOCS3 in the liver by adenovirus or membrane permeable recombinant protein protected the liver from various injuries. However it remained uncertain in which type of cells SOCS3 suppresses liver injury. In this study, we demonstrated that forced expression of SOCS3 in T and NKT cells suppressed ConA-induced hepatitis using T and NKT cell-specific SOCS3 transgenic (Lck-SOCS3 Tg) mice. IFN-\u03b3 and IL-4 production was reduced in Lck-SOCS3 Tg mice as well as splenocytes treated with ConA. IFN-\u03b3 and IL-4 levels were also reduced in Lck-SOCS3 Tg mice administrated with \u03b1-galactosylceramide, suggesting that SOCS3 in NKT cells has suppressive function. Sustained expression of SOCS3 in an NKT cell line also resulted in reduced expression of various cytokines and transcription factors. In contrast, T and NKT cell-specific SOCS3 conditional knockout (Lck-SOCS3 cKO) mice were hypersensitive to ConA-mediated hepatitis. Isolated SOCS3-deficient NKT cells produced higher levels of IFN-\u03b3 and IL-4. These data indicate that SOCS3 plays a negative regulatory role in NKT cell activation and that forced expression of SOCS3 in NKT cells is effective in preventing hepatitis.<\/jats:p>","DOI":"10.4049\/jimmunol.0900547","type":"journal-article","created":{"date-parts":[[2009,11,13]],"date-time":"2009-11-13T21:10:48Z","timestamp":1258146648000},"page":"7047-7053","source":"Crossref","is-referenced-by-count":38,"title":["SOCS3 in T and NKT Cells Negatively Regulates Cytokine Production and Ameliorates ConA-Induced Hepatitis"],"prefix":"10.1093","volume":"183","author":[{"given":"Mako","family":"Nakaya","sequence":"first","affiliation":[{"name":"Department of Biomolecular Sciences, Faculty of Medicine, Saga University , 5-1-1 Nabeshima, Saga,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi , Shinjuku-ku, Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryusuke","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi , Shinjuku-ku, Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wakabayashi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi , Shinjuku-ku, Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuma","family":"Ishizaki","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi , Shinjuku-ku, Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi , Shinjuku-ku, Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Komai","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi , Shinjuku-ku, Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, Faculty of Medicine, Saga University , 5-1-1 Nabeshima, Saga,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiko","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi , Shinjuku-ku, Tokyo,","place":["Japan"]},{"name":"Japan Science and Technology Agency, Core Research for Evolutional Science and Technology , Chiyoda-ku, Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,12,1]]},"reference":[{"key":"2026012811234820800_R1","first-page":"12","article-title":"Brain edema in acute liver failure: a window to the pathogenesis of hepatic encephalopathy.","volume-title":"Ann. 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