Kovats Susan
Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, United States.
Cell Immunol. 2015 Apr;294(2):63-9. doi: 10.1016/j.cellimm.2015.01.018. Epub 2015 Feb 7.
Humans show strong sex differences in immunity to infection and autoimmunity, suggesting sex hormones modulate immune responses. Indeed, receptors for estrogens (ERs) 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.
人类在抗感染免疫和自身免疫方面表现出强烈的性别差异，这表明性激素会调节免疫反应。事实上，雌激素受体（ERs）可调节先天性和适应性免疫系统中的细胞和信号通路，以及免疫细胞的发育。ERs是配体依赖性转录因子，介导远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。ERs还参与膜启动的类固醇信号传导以产生快速反应。雌二醇和ER活性对先天性免疫信号通路和髓样细胞发育具有深刻的剂量和背景依赖性影响。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性信号通路可能会因ER活性而增强或受到抑制。ERs对先天性免疫细胞和信号传导的调节可能导致了所报道的先天性免疫途径中的性别差异。在此，我们综述了近期文献，并强调了ERs调节先天性免疫细胞发育或功能反应的几种分子机制。
