title: The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-β and suppresses T(H)2 differentiation.
abstract: Sox4 is a transcription factor that regulates various developmental processes. Here we show that Sox4 was induced by TGF-β and negatively regulated the transcription factor GATA-3, the master regulator of function of T helper type 2 (T(H)2) cells, by two distinct mechanisms. First, Sox4 bound directly to GATA-3, preventing its binding to GATA-3 consensus DNA sequences. Second, Sox4 bound to the promoter region of the gene encoding interleukin 5 (IL-5), a T(H)2 cytokine, and prevented binding of GATA-3 to this promoter. T(H)2 cell-driven airway inflammation was modulated by alterations in Sox4 expression. Thus, Sox4 acted as a downstream target of TGF-β to inhibit GATA-3 function, T(H)2 differentiation and T(H)2 cell-mediated inflammation.
authors: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Makoto
authors: M
authors: Kuwahara
authors: Masakatsu
authors: M
authors: Yamashita
authors: Kenta
authors: K
authors: Shinoda
authors: Soichi
authors: S
authors: Tofukuji
authors: Atsushi
authors: A
authors: Onodera
authors: Ryo
authors: R
authors: Shinnakasu
authors: Shinichiro
authors: S
authors: Motohashi
authors: Hiroyuki
authors: H
authors: Hosokawa
authors: Damon
authors: D
authors: Tumes
authors: Chiaki
authors: C
authors: Iwamura
authors: Veronique
authors: V
authors: Lefebvre
authors: Toshinori
authors: T
authors: Nakayama
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D055751:SOXC Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015848:Interleukin-5; D034741:RNA, Small Interfering; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma