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

Takeshi Egawa, Robert E. Tillman, Yoshinori Naoe, Ichiro Taniuchi, Dan R. Littman

Research output: Contribution to journalArticlepeer-review

231 Scopus citations

Abstract

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. JEM

Original languageEnglish
Pages (from-to)1945-1957
Number of pages13
JournalJournal of Experimental Medicine
Volume204
Issue number8
DOIs
StatePublished - Aug 6 2007

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