title: Sox5 and c-Maf cooperatively induce Th17 cell differentiation via RORγt induction as downstream targets of Stat3.
abstract: Stat3 signaling is essential for the induction of RORγt and subsequent Th17 cell differentiation. However, the downstream targets of Stat3 for RORγt expression remain largely unknown. We show here that a novel isoform of Sox5, named Sox5t, is induced in Th17 cells in a Stat3-dependent manner. In vivo, T cell-specific Sox5-deficient mice exhibit impaired Th17 cell differentiation and are resistant to experimental autoimmune encephalomyelitis and delayed-type hypersensitivity. Retrovirus-mediated induction of Sox5 together with c-Maf induces Th17 cell differentiation even in Stat3-deficient CD4(+) T cells but not in RORγt-deficient CD4(+) T cells, indicating that Sox5 and c-Maf induce Th17 cell differentiation as downstream effectors of Stat3 and as upstream inducers of RORγt. Moreover, Sox5 physically associates with c-Maf via the HMG domain of Sox5 and DNA-binding domain of c-Maf, and Sox5 together with c-Maf directly activates the promoter of RORγt in CD4(+) T cells. Collectively, our results suggest that Sox5 and c-Maf cooperatively induce Th17 cell differentiation via the induction of RORγt as downstream targets of Stat3.
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors: Shigeru
authors: S
authors: Tanaka
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan suaki@faculty.chiba-u.jp nakajimh@faculty.chiba-u.jp.
authors: Akira
authors: A
authors: Suto
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors: Taro
authors: T
authors: Iwamoto
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors: Daisuke
authors: D
authors: Kashiwakuma
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors: Shin-Ichiro
authors: S
authors: Kagami
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors: Kotaro
authors: K
authors: Suzuki
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors: Hiroaki
authors: H
authors: Takatori
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors: Tomohiro
authors: T
authors: Tamachi
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors: Koichi
authors: K
authors: Hirose
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors: Atsushi
authors: A
authors: Onodera
authors: Department of Human Genome Research, Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan.
authors: Junpei
authors: J
authors: Suzuki
authors: Department of Human Genome Research, Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan.
authors: Osamu
authors: O
authors: Ohara
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan Department of Immunology and Host Defenses, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan.
authors: Masakatsu
authors: M
authors: Yamashita
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan Core Research for Evolutional Science and Technology (CREST), Japan science and Technology Agency, Tokyo 102-0076, Japan.
authors: Toshinori
authors: T
authors: Nakayama
authors: Department of Allergy and Clinical Immunology and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan suaki@faculty.chiba-u.jp nakajimh@faculty.chiba-u.jp.
authors: Hiroshi
authors: H
authors: Nakajima
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D005260:Female; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D051257:Proto-Oncogene Proteins c-maf / Q000378:metabolism*; D055755:SOXD Transcription Factors / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D020381:Interleukin-17; D015850:Interleukin-6; C495608:Maf protein, mouse; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D020033:Protein Isoforms; D051257:Proto-Oncogene Proteins c-maf; C539901:Rorc protein, mouse; D055755:SOXD Transcription Factors; D050796:STAT3 Transcription Factor; C089186:Sox5 protein, mouse; C494087:Stat3 protein, mouse