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.
Tao
Yuehong
Y
Children's Hospital, Fudan University, Shanghai, China.
Yang
Yi
Y
Wang
Weiping
W
D000328:Adult; D001565:Benzoates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000166:cytology; D007959:Lymphocyte Culture Test, Mixed; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors; D000072482:Retinoic Acid Receptor alpha; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology*
D001565:Benzoates; D002839:Chromans; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C084904:Ro 41-5253; D014212:Tretinoin