The Journal of Experimental Medicine
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A correction to this article has been published: Egawa et al., J. Exp. Med. 205 (8) 1939
Published online July 23, 2007
doi:10.1084/jem.20070133
The Journal of Experimental Medicine, Vol. 204, No. 8, 1945-1957
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Egawa et al.
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ARTICLE

 The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells

Takeshi Egawa1, Robert E. Tillman1, Yoshinori Naoe3, Ichiro Taniuchi3,4, and Dan R. Littman1,2

1 Molecular Pathogenesis Program and 2 Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016
3 Laboratory for Transcriptional Regulation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan
4 PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan

CORRESPONDENCE Dan R. Littman: littman{at}saturn.med.nyu.edu

Members of the Runx family of transcriptional regulators are required for the appropriate expression of CD4 and CD8 at discrete stages of T cell development. The roles of these factors in other aspects of T cell development are unknown. We used a strategy to conditionally inactivate the genes encoding Runx1 or Runx3 at different stages of thymocyte development, demonstrating that Runx1 regulates the transitions of developing thymocytes from the CD4–CD8– double-negative stage to the CD4+CD8+ double-positive (DP) stage and from the DP stage to the mature single-positive stage. Runx1 and Runx3 deficiencies caused marked reductions in mature thymocytes and T cells of the CD4+ helper and CD8+ cytotoxic T cell lineages, respectively. Runx1-deficient CD4+ T cells had markedly reduced expression of the interleukin 7 receptor and exhibited shorter survival. In addition, inactivation of both Runx1 and Runx3 at the DP stages resulted in a severe block in development of CD8+ mature thymocytes. These results indicate that Runx proteins have important roles at multiple stages of T cell development and in the homeostasis of mature T cells.

Abbreviations used: DN, double negative; DP, double positive; HSA, heat-stable antigen; icTCR, intracellular TCR ß chain; preTCR, pre–T cell receptor; SP, single positive.


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