The immune system functions in a sexually dimorphic manner, with females exhibiting more robust immune responses than males. However, how female sex hormones affect immune function in normal homeostasis and in autoimmunity is poorly understood. In this review, we discuss how estrogens affect innate and adaptive immune cell activity and how dysregulation of estrogen signaling underlies the pathobiology of some autoimmune diseases and cancers. The potential roles of the major circulating estrogens, and each of the 3 estrogen receptors (ERα, ERβ, and G-protein coupled receptor) in the regulation of the activity of different immune cells are considered. This provides the framework for a discussion of the impact of ER modulators (aromatase inhibitors, selective estrogen receptor modulators, and selective estrogen receptor downregulators) on immunity. Synthesis of this information is timely given the considerable interest of late in defining the mechanistic basis of sex-biased responses/outcomes in patients with different cancers treated with immune checkpoint blockade. It will also be instructive with respect to the further development of ER modulators that modulate immunity in a therapeutically useful manner.

中文翻译：

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免疫系统中的雌激素受体信号。

免疫系统以性别二态的方式发挥作用，女性表现出比男性更强大的免疫反应。然而，女性性激素如何影响正常稳态和自身免疫中的免疫功能知之甚少。在这篇综述中，我们讨论了雌激素如何影响先天性和适应性免疫细胞活性，以及​​雌激素信号传导失调如何成为某些自身免疫性疾病和癌症病理生物学的基础。考虑了主要循环雌激素和 3 种雌激素受体（ERα、ERβ 和 G 蛋白偶联受体）在调节不同免疫细胞活性中的潜在作用。这为讨论 ER 调节剂（芳香酶抑制剂、选择性雌激素受体调节剂和选择性雌激素受体下调剂）对免疫力的影响提供了框架。考虑到最近人们对确定接受免疫检查点阻断治疗的不同癌症患者的性别偏向反应/结果的机制基础产生了相当大的兴趣，因此对这些信息的综合是及时的。对于以治疗有用的方式调节免疫的 ER 调节剂的进一步开发也将具有指导意义。