Runx1 is required for T cell maturation (HEM2P.246)

Abstract

Abstract T cell development depends on coordinated gene expression changes in order to progress through developmental checkpoints. The loss of transcription factor Runx1 in CD4-cre Runx1 conditional knockout (cKO) mice leads to decreased numbers of CD4 single positive (SP) thymocytes, CD4 peripheral T cells and lower expression of IL-7Rα, a key player of T cell homeostasis, by CD4+ Runx1 deficient T cells . Low IL-7Rα is thought to cause decreased CD4 T cell survival. However, we show that constitutive expression of an IL-7Rα transgene in CD4-cre Runx1 cKO mice does not restore thymic or peripheral CD4 cellularity. We also see similar expression of Bcl-2 and Bcl-xL in WT and Runx1-deficient CD4 T cells, indicating that a Runx1-mediated IL-7Rα-independent mechanism might be responsible. As IL-7Rα expression increases over the course of T cell maturation, we asked if Runx1 is needed for maturation. During thymic maturation, post-positive selection CD4 SP thymocytes migrate from cortex to medulla, changing from CCR7lowCD24high to CCR7highCD24high and finally CCR7highCD24low before thymic egress. We saw a block at the CCR7lowCD24high stage in CD4-cre Runx1 cKO CD4 SP thymocytes. Additionally, other maturation markers including CD55 and Qa2 were also downregulated. Thus, Runx1 is required for thymic maturation of CD4 SP thymocytes.