Estrogen receptors regulate innate immune cells and signaling pathways.

Estrogen receptors regulate innate immune cells and signaling pathways.
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DOI:
10.1016/j.cellimm.2015.01.018
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发表时间:
2015-04
影响因子:
4.3
通讯作者:
Kovats S
Kovats S
中科院分区:
医学4区
文献类型:
--
作者:
Kovats S

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人类在对感染和自身免疫的免疫力方面表现出强烈的性别差异,这表明性激素调节免疫反应。事实上,雌激素受体(ER)调节先天性和适应性免疫系统中的细胞和途径,以及免疫细胞发育。ER是配体依赖性转录因子,其介导长距离染色质相互作用并在基因调控元件处形成复合物,从而促进表观遗传变化和转录。ER还参与膜启动的类固醇信号传导以产生快速反应。雌激素受体和雌激素受体活性对先天免疫信号传导途径和骨髓细胞发育显示出深刻的剂量和环境依赖性作用。虽然雌二醇最常促进I型干扰素的产生,但导致促炎细胞因子产生的先天途径可通过ER活性增强或抑制。ER对先天免疫细胞和信号传导的调节可能有助于先天免疫途径中报告的性别差异。在这里,我们回顾了最近的文献,并强调了ER调节先天免疫细胞的发育或功能反应的几种分子机制。
Humans show strong sex differences in immunity to infection and autoimmunity, suggesting sex hormones modulate immune responses. Indeed, receptors for estrogens (ER) regulate cells and pathways in the innate and adaptive immune system, as well as immune cell development. ERs are ligand-dependent transcription factors that mediate long-range chromatin interactions and form complexes at gene regulatory elements, thus promoting epigenetic changes and transcription. ERs also participate in membrane-initiated steroid signaling to generate rapid responses. Estradiol and ER activity show profound dose- and context-dependent effects on innate immune signaling pathways and myeloid cell development. While estradiol most often promotes the production of type I interferon, innate pathways leading to pro-inflammatory cytokine production may be enhanced or dampened by ER activity. Regulation of innate immune cells and signaling by ERs may contribute to the reported sex differences in innate immune pathways. Here we review the recent literature and highlight several molecular mechanisms by which ERs regulate the development or functional responses of innate immune cells.
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