Regulation of alphabeta/gammadelta 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 gammadelta T cells, whereas alphabeta T cell development was partially arrested at the double-negative 3 stage. The increased generation of gammadelta T cells by loss of c-Jun was cell autonomous, because in a competitive reconstitution experiment the knockout-derived cells produced more gammadelta T cells than did the control cells. C-jun-deficient immature T cells failed to efficiently repress transcription of IL-7Ralpha, resulting in augmented IL-7Ralpha mRNA and surface levels. Chromatin immunoprecipitation assays revealed binding of c-Jun to AP-1 binding sites present in the IL-7Ralpha promoter, indicating direct transcriptional regulation. Thus, c-Jun controls the transcription of IL-7Ralpha and is a novel regulator of the alphabeta/gammadelta T cell development.