雌二醇调节树突状细胞功能参与狼疮鼠的发病机制

The role of estrogen in the pathogenesis of lupus in NZB/w F1 mice by modulating the function of dendritic cells

目的比较雌二醇（E2）对SLE模型鼠-（NZBxNZW）FI（NZB／wFI）雌鼠发病前后脾脏树突状细胞（DC）的影响，探索雌激素对DC的调节是否和系统性红斑狼疮（SLE）的进展相关。方法抗CD11c单抗标记的免疫磁珠纯化DC，流式细胞仪检测DC表面分子和细胞因子，混合淋巴细胞反应检测DC对脾脏T细胞的刺激功能，半定量反转录-聚合酶链反应（RT—PCR）法检测DC内雌激素受体（ER）的表达。结果E2影响狼疮鼠脾脏DC的CD40、白细胞介素（IL）-6、IL-10、IL-12、肿瘤坏死因子（TNF）-α和ERd的表达及刺激活性；枸橼酸他莫西芬（TAM）拮抗E2的作用；E2对不同周龄鼠DC的作用不同。结论E2通过与DC的ERα结合而调控DC来参与SLE的病理机制，E2对DC的作用和病程进展有关。

Objective To investigate the effect of estrogen on dendritic cells （DCs） and its role in disease progression by comparing the effects of 17β-estradiol （E2） on spleen DCs in systemic lupus erythematosus （SLE） murine model-（NZB×NZW） FI （NZB/w F I ） female mice before and after the disease onset. Methods Anti-CDllc antibody labeled magnetic bead was used to purify spleen DCs. Flow cytometry was utilized to detect the co-stimulatory molecules and intracellular cytokines of DCs. Mixed lymphocytes reaction （MLR） was used to measure the stimulatory activity of DCs to T lymphocytes. And semi-quantitative RT-PCR was employed to check the expression of estrogen receptor （ER）. Results E2 could modulate the expression of surface molecule CD40, the production of cytokines IL-6, IL-10, IL-12 and TNFα, and the stimulatory a- bility of spleen DCs in SLE model mice. Tamoxifen （TAM） could antagonize E2 effects and E2 could affect the estrogen receptor （ERa） level of DCs. These changes of DCs varied with age. Conclusion E2 may be involved in the pathogenesis of SLE by modulating DCs by binding ERα. The effects of E2 vary in different stages of SLE progression.