17beta-estradiol enhances the response of plasmacytoid dendritic cell to CpG.
17beta-estradiol enhances the response of plasmacytoid dendritic cell to CpG.
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DOI：
10.1371/journal.pone.0008412
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发表时间：
2009-12-23
期刊：
影响因子：
3.7
通讯作者：
Hou Y
中科院分区：
文献类型：
--
作者：
Li X;Xu Y;Ma L;Sun L;Fu G;Hou Y
免疫能力的性别差异表明，雌激素等性激素参与了免疫能力的调节。大量研究也表明，浆细胞样树突状细胞(PDCs)在SLE中起致病作用。然而，雌激素是否能调节PDCs的功能从而影响SLE的发生发展，目前尚不清楚。本研究采用17-雌二醇(17β-estadiol，E_2)和环磷酰胺(CpG)单独或联合作用于小鼠脾来源的PDCs，分析其细胞活力、共刺激分子表达、细胞因子分泌以及对B细胞的刺激作用。结果表明，E_2和CpG协同作用可提高PDCs的细胞活力和共刺激分子的表达。此外，E_2或E_2+CpG均能增加细胞内外干扰素-α的分泌。此外，E_2和CpG还可增强PDCs对B细胞的刺激能力，且中和干扰素-α后B细胞的活性显著降低。在体内实验中，小鼠每日皮下注射。单独或同时注射E_2和CpG后，发现E_2和Cp G协同作用可提高小鼠血浆免疫球蛋白M浓度，与E_2或Cp G单独作用相比，Cp G加E_2能显著增加脾组织中干扰素-α/β的表达。本研究表明，雌二醇可加剧PDC对CpG的激活，进而激活B细胞，上调自身抗原的易感性。干扰素-α在PDCs对B细胞的刺激作用中起重要作用。E2刺激干扰素-α的产生可能通过激活PDCs而导致女性在系统性红斑狼疮等自身免疫性疾病中的流行。这项研究为雌激素与系统性红斑狼疮的关系提供了新的证据，也揭示了系统性红斑狼疮患者中的性别偏见。
Gender differences in immune capabilities suggest that sex hormones such as estrogens were involved in the regulation of the immunocompetence. Numerous studies also suggest that plasmacytoid dendritic cells (PDCs) play a pathogenic role in SLE. However, it is unclear whether estrogen can modulate the function of PDCs to influence the development of SLE. In the present study, PDCs from murine spleens were treated with 17β-estradiol (E2) and CpG respectively or both in vitro, then cell viability, costimulatory molecule expression, cytokine secretion of PDCs, as well as stimulatory capacity of PDCs to B cells were analyzed. Results showed that E2 and CpG increased the cell viability and costimulatory molecule expression on PDCs synergistically. Moreover, the intracellular and extracellular secretion of IFN-α was increased by E2 or E2 plus CpG. In addition, E2 and CpG also increased the stimulatory capacity of PDCs to B cells, and the viability of B cells was decreased after neutralizing IFN-α significantly. In the experiments in vivo, mice received daily s.c. injections of E2 and CpG respectively or both, then we found that the plasma concentration of IgM were elevated by E2 and CpG synergistically and the expression of IFN-α/β in spleens were noticeably increased by CpG plus E2 compared with the treatment of E2 or CpG only. This study indicates that E2 could exacerbate PDCs' activation with CpG, which further activates B cells to upregulate susceptibility to autoantigens. IFN-α plays an important role in the stimulatory effect of PDCs on B cells. E2 stimulation of IFN-α production may result in female prevalence in autoimmune diseases such as SLE through activation of PDCs. This study provides novel evidence of relationship between estrogen and SLE and also sheds light on gender biases among SLE patients.