{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:42:15Z","timestamp":1791103335052,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2008,3,1]],"date-time":"2008-03-01T00:00:00Z","timestamp":1204329600000},"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":[[2008,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Suppressor of cytokine signaling 1 (SOCS1) is an important negative regulator for cytokines; however, the role of SOCS1 in Th17 differentiation has not been clarified. We generated T cell-specific SOCS1-deficient mice and found that these mice were extremely resistant to a Th17-dependent autoimmune disease model, experimental autoimmune encephalomyelitis. SOCS1-deficient naive CD4+ T cells were predominantly differentiated into Th1 and poorly into Th17 in vitro. These phenotypes were canceled in IFN-\u03b3\u2212\/\u2212 background, suggesting that a large amount of IFN-\u03b3 in SOCS1-deficient T cells suppressed Th17 differentiation. IL-6 plus TGF-\u03b2 enhanced retinoic acid receptor-related orphan receptor (ROR)-\u03b3t expression and suppressed IFN-\u03b3 production in wild-type T cells, whereas these effects were severely impaired in SOCS1-deficient T cells. These phenotypes can be partly explained by STAT3 suppression by enhanced SOCS3 induction through hyper-STAT1 activation in SOCS1-deficient T cells. In addition, SOCS1-deficient T cells were much less sensitive to TGF-\u03b2. Suppression of Th1 differentiation by TGF-\u03b2 was impaired in SOCS1-deficient T cells. TGF-\u03b2-mediated Smad transcriptional activity was severely inhibited in SOCS1-deficient cells in the presence of IFN-\u03b3. Such impairment of TGF-\u03b2 functions were not observed in SOCS3-overexpressed cells, indicating that suppression of Smads was independent of SOCS3. Therefore, SOCS1 is necessary for Th17 differentiation by suppressing antagonistic effect of IFN-\u03b3 on both STAT3 and Smads. Induction of SOCS3 can partly explain IFN-\u03b3-mediated STAT3 suppression, while other mechanism(s) will be involved in IFN-\u03b3-mediated Smad suppression. SOCS1-deficient T cells will be very useful to investigate the molecular mechanism for the STAT1-mediated suppression of Th17 development.<\/jats:p>","DOI":"10.4049\/jimmunol.180.6.3746","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:47:10Z","timestamp":1397850430000},"page":"3746-3756","source":"Crossref","is-referenced-by-count":159,"title":["Loss of Suppressor of Cytokine Signaling 1 in Helper T Cells Leads to Defective Th17 Differentiation by Enhancing Antagonistic Effects of IFN-\u03b3 on STAT3 and Smads"],"prefix":"10.1093","volume":"180","author":[{"given":"Kentaro","family":"Tanaka","sequence":"first","affiliation":[{"name":"Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka"},{"name":"Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Ichiyama","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohito","family":"Takimoto","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giichi","family":"Takaesu","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Torisu","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikatsu","family":"Hanada","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka"},{"name":"Institute of Molecular Biotechnology , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Yasukawa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiovascular Research Institute, Kurume University School of Medicine , Kurume ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Fukuyama","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka"},{"name":"Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Inoue","sequence":"additional","affiliation":[{"name":"Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,3,15]]},"reference":[{"key":"2026012809130543200_R1","first-page":"145","volume-title":"Annu. 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