The Journal of Experimental Medicine
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Published online 30 June 2003 doi:10.1084/jem.20021200
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© Rockefeller University Press, 0022-1007/2003/7/51 $5.00
The Journal of Experimental Medicine, Volume 198, Number 1, 51-61

The Runx1 Transcription Factor Inhibits the Differentiation of Naive CD4+ T Cells into the Th2 Lineage by Repressing GATA3 Expression

Okiru Komine1, Keitaro Hayashi2, Waka Natsume2, Toshio Watanabe2, Youichi Seki1, Noriyasu Seki1, Ryoji Yagi1, Wataru Sukzuki1, Hidekazu Tamauchi3, Katsuto Hozumi4, Sonoko Habu4, Masato Kubo1 and Masanobu Satake2

1 Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda 278-0022, Japan
2 Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan
3 Department of Microbiology plus Parasitology, School of Medicine, Kitasato University, Sagamihara 228-8555, Japan
4 Department of Immunology, Tokai University School of Medicine, Boseidai, Isehara 259-1193, Japan

Address correspondence to Masanobu Satake, Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Phone: 81-22-717-8481; Fax: 81-22-717-8482; E-mail: satake{at}idac.tohoku.ac.jp; or Masato Kubo, Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda 278-0022, Japan. Phone: 81-4-7121-4060; Fax: 81-4-7121-4069; E-mail: raysolfe{at}rs.noda.tus.ac.jp

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.

Key Words: GATA3 • Runx1 • Th2 • T lymphocytes • transcription factor


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