The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells.
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.
Egawa
Takeshi
T
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
Tillman
Robert E
RE
Naoe
Yoshinori
Y
Taniuchi
Ichiro
I
Littman
Dan R
DR
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D015851:Interleukin-7 / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism
D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D015851:Interleukin-7; C493726:Runx1 protein, mouse