Relevance of sexual dimorphism to regulatory T cells:: estradiol promotes IFN-γ production by invariant natural killer T cells
Relevance of sexual dimorphism to regulatory T cells:: estradiol promotes IFN-γ production by invariant natural killer T cells
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DOI：
10.1182/blood-2004-07-2819
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发表时间：
2005-03-15
期刊：
影响因子：
20.3
通讯作者：
Herbelin, A
中科院分区：
文献类型：
--
作者：
Gourdy, P;Araujo, LM;Herbelin, A
在免疫反应中性别二态性的机制仍然知之甚少。由于不变的自然杀伤T（iNKT）细胞通过产生辅助性T细胞1（Th 1）和Th 2细胞因子的能力发挥重要的调节功能，我们解决了这些活动是否可以通过性激素调节的问题。我们发现，在体内的挑战与iNKT细胞的特异性配体，α-半乳糖神经酰胺（α-GalCer），诱导显着更高浓度的干扰素γ（IFN-γ）的血清中的女性比男性小鼠，而白细胞介素4（IL-4）的生产没有修改。为了支持卵巢激素在这一现象中的关键作用，在卵巢切除的女性中发生血清IFN-γ浓度的显著降低，以响应α-GalCer治疗，而卵巢切除术既不影响男性中的IFN-γ也不影响IL-4血清浓度。雌激素在iNKT细胞产生IFN-γ的这种选择性增强中的作用通过以下方式证明：（1）在体外和体内暴露于雌二醇时，iNKT细胞的α-GalCer诱导的IFN-γ合成增加，和（2）在雌激素受体α缺陷小鼠中α-GalCer诱导的IFN-γ释放中的性别连锁差异消除。这些结果提供了雌激素影响iNKT细胞的第一个证据，导致其细胞因子产生谱的性别二态性。(c)2005年，美国血液学会。
Mechanisms accounting for gender dimorphism during immune responses are still poorly understood. Since invariant natural killer T (iNKT) cells exert important regulatory functions through their capacity to produce both T helper 1 (Th1) and Th2 cytokines, we addressed the question of whether these activities could be modulated by sexual hormones. We found that in vivo challenge with the specific ligand of iNKT cells, alpha-galactosylceramide (alpha-GalCer), induced significantly higher concentrations of interferon gamma (IFN-gamma) in the serum of female than in that of male mice, while interleukin 4 (IL-4) production was not modified. In support of a crucial role of ovarian hormones in this phenomenon, a significant decrease of serum IFN-gamma concentrations occurred in ovariectomized females, in response to treatment with alpha-GalCer, while orchidectomy affected neither IFN-gamma nor IL-4 serum concentrations in males. The implication of estrogens in this selective enhancement of IFN-gamma production by iNKT cells was demonstrated by (1) the increased alpha-GalCer-induced IFN-gamma synthesis by iNKT cells upon both in vitro and in vivo exposure to estradiol and (2) the abolition of the sex-linked difference in alpha-GalCer-induced IFN-gamma release in estrogen receptor alpha-deficient mice. These results provide the first evidence that estrogens influence iNKT cells leading to this gender dimorphism in their cytokine production profile. (c) 2005 by The American Society of Hematology.