Effect of all-trans-retinoic acid on the differentiation, maturation and functions of dendritic cells derived from cord blood monocytes.

We investigated the effects of all-trans-retinoic acid on dendritic cells derived from human cord blood monocytes to clarify how vitamin A affects immune function in children. Monocytes were separated from 18 cord blood samples, and dendritic cells were differentiated by culture. The percentage of dendritic cells was markedly lower in all-trans-retinoic acid treated cells than in untreated cells. After exposure to tumour necrosis factor-alpha for 3 days, all-trans-retinoic acid treated dendritic cells showed a reduced capacity to activate alloreactive T cells compared to untreated cells. In addition, all-trans-retinoic acid-treated dendritic cells could drive T cells towards T-helper cell type 2 responses with decreased secretion of interleukin-12, interferon-gamma, and increased production of interleukin-10 and interleukin-4. However, when Ro 41-5253, a selective retinoic acid receptor alpha antagonist, was add to culture, all the above actions were reversed. Thus, all-trans-retinoic acid may act at the first step of the immune response by inhibiting the differentiation of dendritic cells, maturation and induction of the T-helper cell type-2 response. The actions of all-trans-retinoic acid on dendritic cells were mediated through retinoic acid receptor alpha.