Regulation of αβ/γδ T Cell Development by the Activator Protein 1 Transcription Factor c-Jun

Abstract

c-Jun is a member of the AP-1 family of transcription factors, the activity of which is strongly augmented by TCR signaling. To elucidate the functions of c-Jun in mouse thymic lymphopoiesis, we conditionally inactivated c-Jun specifically during early T cell development. The loss of c-Jun resulted in enhanced generation of γδ T cells, whereas αβ T cell development was partially arrested at the double-negative 3 stage. The increased generation of γδ T cells by loss of c-Jun was cell autonomous, because in a competitive reconstitution experiment the knockout-derived cells produced more γδ T cells than did the control cells. C-jun-deficient immature T cells failed to efficiently repress transcription of IL-7Rα, resulting in augmented IL-7Rα mRNA and surface levels. Chromatin immunoprecipitation assays revealed binding of c-Jun to AP-1 binding sites present in the IL-7Rα promoter, indicating direct transcriptional regulation. Thus, c-Jun controls the transcription of IL-7Rα and is a novel regulator of the αβ/γδ T cell development.