THE EFFECT OF RETINOIC ACID ON DENDRITIC CELL DERIVED FROM CORD BLOOD AND ITS PATHWAY

Objective: To investigate the role of retinoic acid (RA) in the differentiation, and maturation of dendritic cells (DCs) derived from cord blood monocytes, and its mechanism. Method: Nine cord blood samples were collected from healthy and well nourished newborns. Monocytes were isolated and cultured in vitro. Cells were divided into 4 groups: control group; retinoid acid receptor α (RARα )agonist group (RA group); RARα antagonist group (RO group) and agonist plus antagonist group (RA+RO group). Part cells were collected in D9, and the surface markers on cells were detected by flow cytometer. The mixed lymphocyte reaction (allo-MLR) was used to evaluate the ability of DC to induce proliferation of T cells and the influence by RA and RARα. Th cytokines were measured in protein level by ELISA and in mRNA levels by RT-PCR to decipher the effect of RA and RARα in the regulation of Th1/Th2 balance by DCs. Results: The differentiation and maturation of DCs were inhibited significantly in RA group compared with control group. When RO was added into the culture, the effects of RA can be reversed. After MLR , the suppression effect of RA on allo-T cell proliferation was inversed by RO. During the influence of DC on Th cell polarization, RO could inhibit the down-regulation of Th1 cytokine (IFN-γ) as well as the up- regulation of Th2 cytokines (IL-4, IL-10) by RA, whether on protein levels or on mRNA levels. Conclusion: Retinoic acid inhibited the differentiation and maturation of DC derived from cord blood monocytes, reduced the ability to stimulate allo-T lymphocytes proliferation by DCs, and made immune response bias to Th2. RARα plays a very important role in the regulation of RA on DCs.