A crucial role for retinoic acid in the development of N otch‐dependent murine splenic CD 8− CD 4− and CD 4+ dendritic cells

This is the authors' abstract. We don't add key points for this paper.

The vitamin A metabolite retinoic acid is important for the function of the adaptive immune system, but the mechanism is not completely understood. Here we show that vitamin A is essential for the generation of Notch-dependent CD8(-) dendritic cells (DCs) in the spleen. We observed that CD8(-) CD4(-) (double negative (DN)) and CD4(+) DCs, but not CD8(+) DCs, express vitamin A regulated genes. To determine whether vitamin A levels influence splenic DC development, we generated mice that were fed a vitamin A-deficient diet. We detected a specific reduction of CD4(+) and DN DCs in the spleens of mice fed a vitamin A-deficient diet, while pre-DC numbers in both spleen and bone marrow were not affected. Vitamin A was specifically necessary for the development of RelB(high) , Notch-dependent CD4(+) , and DN DCs. In addition, DN DCs showed reduced proliferation during vitamin A deficiency. In contrast, mice that had received a diet with increased amounts of retinoic acid showed a significant expansion of Notch-dependent DN DCs. These data demonstrate that vitamin A stimulates the development of Notch-dependent splenic DCs and indicate that inefficient generation of DCs may contribute to the immune deficits observed during vitamin A deficiency.