Essential Role for Retinoic Acid in the Promotion of CD4+ T Cell Effector Responses via Retinoic Acid Receptor Alpha

Abstract

Vitamin A and its metabolite, retinoic acid (RA) are implicated in the regulation of immune homeostasis via the peripheral induction of regulatory Tcells. Here we showed RA was also required to elicit proinflammatory CD4(+) helper Tcell responses to infection and mucosal vaccination. Retinoic acid receptor alpha (RARα) was the critical mediator of these effects. Antagonism of RAR signaling and deficiency in RARα (Rara(-/-)) resulted in a cell-autonomous CD4(+) Tcell activation defect, which impaired intermediate signaling events, including calcium mobilization. Altogether, these findings reveal a fundamental role for the RA-RARα axis in the development of both regulatory and inflammatory arms of adaptive immunity and establish nutritional status as a broad regulator of adaptive Tcell responses.