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We show here that during Th1 differentiation a reduction in the association of Janus kinase 1 with the IL-4 receptor (IL-4R) correlated with the appearance of the suppressor of cytokine signaling-5 (SOCS5). SOCS5 protein was preferentially expressed in committed Th1 cells and interacted with the cytoplasmic region of the IL-4R\u03b1 chain irrespective of receptor tyrosine phosphorylation. This unconventional interaction of SOCS5 protein with the IL-4R resulted in the inhibition of IL-4-mediated signal transducer and activator of transcription-6 activation. T cells from transgenic mice constitutively expressing SOCS5 exhibited a significant reduction of IL-4-mediated Th2 development. Therefore, the induced SOCS5 protein in Th1 differentiation environment may play an important role by regulating Th1 and Th2 balance.<\/jats:p>","DOI":"10.1073\/pnas.202477099","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T12:58:07Z","timestamp":1033477087000},"page":"13003-13008","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":169,"title":["Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation"],"prefix":"10.1073","volume":"99","author":[{"given":"Yoh-ichi","family":"Seki","sequence":"first","affiliation":[{"name":"Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan; Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Umaide, Higashi-hu Fukuoka 812-8582, Japan; Novasite Pharmaceuticals, 11095 Flintkote Avenue, San Diego, CA 92121-1194; and Department of Molecular Medicine, Osaka University Graduate School of Medicine and Osaka University, 1-1 Yamada-cho, Suita City, Osaka 565-0871, Japan"}]},{"given":"Katsuhiko","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan; Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Umaide, Higashi-hu Fukuoka 812-8582, Japan; Novasite Pharmaceuticals, 11095 Flintkote Avenue, San Diego, CA 92121-1194; and Department of Molecular Medicine, Osaka University Graduate School of Medicine and Osaka University, 1-1 Yamada-cho, Suita City, Osaka 565-0871, Japan"}]},{"given":"Akira","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan; Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Umaide, Higashi-hu Fukuoka 812-8582, Japan; Novasite Pharmaceuticals, 11095 Flintkote Avenue, San Diego, CA 92121-1194; and Department of Molecular Medicine, Osaka University Graduate School of Medicine and Osaka University, 1-1 Yamada-cho, Suita City, Osaka 565-0871, Japan"}]},{"given":"Noriyasu","family":"Seki","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan; Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Umaide, Higashi-hu Fukuoka 812-8582, Japan; Novasite Pharmaceuticals, 11095 Flintkote Avenue, San Diego, CA 92121-1194; and Department of Molecular Medicine, Osaka University Graduate School of Medicine and Osaka University, 1-1 Yamada-cho, Suita City, Osaka 565-0871, Japan"}]},{"given":"Jun","family":"Tsukada","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan; Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Umaide, Higashi-hu Fukuoka 812-8582, Japan; Novasite Pharmaceuticals, 11095 Flintkote Avenue, San Diego, CA 92121-1194; and Department of Molecular Medicine, Osaka University Graduate School of Medicine and Osaka University, 1-1 Yamada-cho, Suita City, Osaka 565-0871, Japan"}]},{"given":"John","family":"Ransom","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan; Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Umaide, Higashi-hu Fukuoka 812-8582, Japan; Novasite Pharmaceuticals, 11095 Flintkote Avenue, San Diego, CA 92121-1194; and Department of Molecular Medicine, Osaka University Graduate School of Medicine and Osaka University, 1-1 Yamada-cho, Suita City, Osaka 565-0871, Japan"}]},{"given":"Tetsuji","family":"Naka","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan; Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Umaide, Higashi-hu Fukuoka 812-8582, Japan; Novasite Pharmaceuticals, 11095 Flintkote Avenue, San Diego, CA 92121-1194; and Department of Molecular Medicine, Osaka University Graduate School of Medicine and Osaka University, 1-1 Yamada-cho, Suita City, Osaka 565-0871, Japan"}]},{"given":"Tadamitsu","family":"Kishimoto","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan; Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Umaide, Higashi-hu Fukuoka 812-8582, Japan; Novasite Pharmaceuticals, 11095 Flintkote Avenue, San Diego, CA 92121-1194; and Department of Molecular Medicine, Osaka University Graduate School of Medicine and Osaka University, 1-1 Yamada-cho, Suita City, Osaka 565-0871, Japan"}]},{"given":"Akihiko","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan; Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Umaide, Higashi-hu Fukuoka 812-8582, Japan; Novasite Pharmaceuticals, 11095 Flintkote Avenue, San Diego, CA 92121-1194; and Department of Molecular Medicine, Osaka University Graduate School of Medicine and Osaka University, 1-1 Yamada-cho, Suita City, Osaka 565-0871, Japan"}]},{"given":"Masato","family":"Kubo","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan; Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Umaide, Higashi-hu Fukuoka 812-8582, Japan; Novasite Pharmaceuticals, 11095 Flintkote Avenue, San Diego, CA 92121-1194; and Department of Molecular Medicine, Osaka University Graduate School of Medicine and Osaka University, 1-1 Yamada-cho, Suita City, Osaka 565-0871, 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