Vitamin A is an essential nutrient that is critical for human health. Recent findings indicate that metabolites of vitamin A, namely retinoic acid, exert immunoregulatory effects through the induction of regulatory T cells and, independently, though suppression of effector T cell responses. However, the paramount role of this vitamin in sustaining protective immunity in humans has not been integrated into these findings. We found that vitamin A deficiency abrogates CD4+ helper T cell type 1 (TH-1) and type 17 (TH-17) immunity to active infection and oral vaccination. Short-term administration of the vitamin A metabolite, retinoic acid (RA), fully restored TH-1 and TH-17 responses in vivo, and this effect was mediated through retinoic acid receptor alpha (RAR-a). Moreover, deficiency in RAR-a;resulted in a cell autonomous CD4+ T cell activation defect. Altogether, our work reveals a novel and essential role for RA in the promotion of vitamin A dependent immunity via direct effects on effector CD4+ T cell function. Our results also establish nutritional status as a tuning mechanism for effector T cell responses.
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