The Runx1 transcription factor inhibits the differentiation of naive CD4+ T cells into the Th2 lineage by repressing GATA3 expression.
Differentiation of naive CD4+ T cells into helper T (Th) cells is controlled by a combination of several transcriptional factors. In this study, we examined the functional role of the Runx1 transcription factor in Th cell differentiation. Naive T cells from transgenic mice expressing a dominant interfering form of Runx1 exhibited enhanced interleukin 4 production and efficient Th2 differentiation. In contrast, transduction of Runx1 into wild-type T cells caused a complete attenuation of Th2 differentiation and was accompanied by the cessation of GATA3 expression. Furthermore, endogenous expression of Runx1 in naive T cells declined after T cell receptor stimulation, at the same time that expression of GATA3 increased. We conclude that Runx1 plays a novel role as a negative regulator of GATA3 expression, thereby inhibiting the Th2 cell differentiation.
Komine
Okiru
O
Research Institute for Biological Sciences, Tokyo University of Science, Noda, Japan.
Hayashi
Keitaro
K
Natsume
Waka
W
Watanabe
Toshio
T
Seki
Youichi
Y
Seki
Noriyasu
N
Yagi
Ryoji
R
Sukzuki
Wataru
W
Tamauchi
Hidekazu
H
Hozumi
Katsuto
K
Habu
Sonoko
S
Kubo
Masato
M
Satake
Masanobu
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D050990:GATA3 Transcription Factor; D015847:Interleukin-4 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D019948:Receptors, Interleukin-4 / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology*
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D019948:Receptors, Interleukin-4; D012097:Repressor Proteins; C493726:Runx1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4