Immunity
Volume 34, Issue 3, 25 March 2011, Pages 435-447
Journal home page for Immunity

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

https://doi.org/10.1016/j.immuni.2011.03.003Get rights and content
Under an Elsevier user license
open archive

Summary

Vitamin A and its metabolite, retinoic acid (RA) are implicated in the regulation of immune homeostasis via the peripheral induction of regulatory T cells. Here we showed RA was also required to elicit proinflammatory CD4+ helper T cell 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+ T cell 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 T cell responses.

Highlights

► Th1 and Th17 cell immunity are abrogated in the absence of vitamin A metabolites ► Retinoic acid rescues Th1 and Th17 immune responses in the absence of vitamin A ► RA receptor alpha is a dominant mediator of CD4+ T cell immunity and homeostasis ► RA receptor-driven signals influence TCR signaling pathways

Cited by (0)