摘要
目的:研究视黄酸(RA)对脐血树突状细胞(dendriticcell,DC)分化、成熟和功能的影响,探讨视黄酸受体(retinoicacidreceptorα,RARα)在RA对脐血DC调节中的作用。方法:收集脐血9份,分离单个核细胞后,均匀分为4组:对照组、RA组、RARα特异性拮抗剂组(RO组)、RA+RO组。在体外进行DC的诱导培养,流式细胞仪检测细胞表面标记及其荧光强度,观察RA及RARα对DC分化、成熟的影响;培养DC与T细胞进行混合淋巴细胞反应(mixedlymphocytereaction,MLR)后,观察RA及RARα对DC刺激异体T细胞增殖能力的作用;采用ELISA法和RT-PCR法研究RA和RARα在DC对Th细胞极向分化调节中的作用。结果:RA使DC的分化、成熟明显受抑,但当RO同时加入时,则可逆转该影响;MLR后发现RO可逆转RA对T细胞增殖的抑制作用;在DC对T细胞极向分化的研究中,无论在蛋白水平还是基因水平,RO均可明显阻止RA对Th1(IFN-γ)的下调和对Th2(IL-4、IL-10)的上调作用。结论:RA抑制体外培养的脐血单个核细胞向DC的分化和成熟,降低其MLR能力,使免疫反应向Th2方向偏移。RARα从多个环节上参与了RA对脐血DC的调节作用。
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 CRO 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 reaotion (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 suooression 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 Thl 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. [ACTA NUTRIMENTA SINICA, 2006, 28(1): 36-391
出处
《营养学报》
CAS
CSCD
北大核心
2006年第1期36-39,共4页
Acta Nutrimenta Sinica
基金
国家自然科学基金(No.30070661)