TY - JOUR
T1 - The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-β and suppresses T H2 differentiation
AU - Kuwahara, Makoto
AU - Yamashita, Masakatsu
AU - Shinoda, Kenta
AU - Tofukuji, Soichi
AU - Onodera, Atsushi
AU - Shinnakasu, Ryo
AU - Motohashi, Shinichiro
AU - Hosokawa, Hiroyuki
AU - Tumes, Damon
AU - Iwamura, Chiaki
AU - Lefebvre, Veronique
AU - Nakayama, Toshinori
N1 - Funding Information:
We thank D. Loh (Washington University School of Medicine) for DO11.10 mice; R. Kubo, A. Singer and D. Singer for comments and criticisms in the preparation of this manuscript; and K. Sugaya, H. Asou, S. Norikane, M. Kato and T. Ito for technical assistance. Supported by the Global Center for Education and Research in Immune System Regulation and Treatment, City Area Program (Kazusa/Chiba Area) of the Ministry of Education, Culture, Sports, Science and Technology of Japan, Japan Science and Technology Agency Core Research for Evolutional Science and Technology, Japan Science and Technology Agency Precursory Research for Embryonic Science and Technology, the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grants-in-Aid for Scientific Research on Priority Areas 22021008 and 22021011; Scientific Research (B) 21390147 and 23390075), the Ministry of Health, Labor and Welfare of Japan, the Uehara Memorial Foundation, the Mochida Foundation, the Naito Foundation and the Takeda Science Foundation.
PY - 2012/8
Y1 - 2012/8
N2 - 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 H2) 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 H2 cytokine, and prevented binding of GATA-3 to this promoter. T H2 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 H2 differentiation and T H2 cell-mediated inflammation.
AB - 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 H2) 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 H2 cytokine, and prevented binding of GATA-3 to this promoter. T H2 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 H2 differentiation and T H2 cell-mediated inflammation.
UR - https://www.scopus.com/pages/publications/84864131152
U2 - 10.1038/ni.2362
DO - 10.1038/ni.2362
M3 - Article
C2 - 22751141
AN - SCOPUS:84864131152
SN - 1529-2908
VL - 13
SP - 778
EP - 786
JO - Nature Immunology
JF - Nature Immunology
IS - 8
ER -