The loss of estrogen (E₂) initiates a rapid phase of bone loss leading to osteoporosis in one‐half of postmenopausal women, but the mechanism is not fully understood. Here, we show for the first time how loss of E₂ activates low‐grade inflammation to promote the acute phase of bone catabolic activity in ovariectomized (OVX) mice. E₂ regulates the abundance of dendritic cells (DCs) that express IL‐7 and IL‐15 by inducing the Fas ligand (FasL) and apoptosis of the DC. In the absence of E₂, DCs become long‐lived, leading to increased IL‐7 and IL‐15. We find that IL‐7 and IL‐15 together, but not alone, induced antigen‐independent production of IL‐17A and TNFα in a subset of memory T cells (T_MEM). OVX of mice with T‐cell–specific ablation of IL15RA showed no IL‐17A and TNFα expression, and no increase in bone resorption or bone loss, confirming the role of IL‐15 in activating the T_MEM and the need for inflammation. Our results provide a new mechanism by which E₂ regulates the immune system, and how menopause leads to osteoporosis. The low‐grade inflammation is likely to cause or contribute to other comorbidities observed postmenopause. © 2020 American Society for Bone and Mineral Research.

中文翻译：

---

卵巢切除术激活由记忆 T 细胞介导的慢性低度炎症，从而促进小鼠骨质疏松症。

雌激素 (E ₂ ) 的流失引发了骨质流失的快速阶段，导致一半绝经后妇女出现骨质疏松症，但其机制尚不完全清楚。在这里，我们首次展示了 E ₂的缺失如何激活低度炎症，从而促进去卵巢 (OVX) 小鼠骨分解代谢活动的急性期。E ₂通过诱导 DC 的 Fas 配体 (FasL) 和凋亡来调节表达 IL-7 和 IL-15 的树突状细胞 (DC) 的丰度。在没有 E ₂的情况下，DC 变得长寿，导致 IL-7 和 IL-15 增加。我们发现 IL-7 和 IL-15 一起（但不是单独）在记忆 T 细胞亚群（T _MEM）。用 T 细胞特异性消融IL15RA的小鼠的 OVX显示没有 IL-17A 和 TNFα 表达，也没有增加骨吸收或骨丢失，证实了 IL-15 在激活 T _MEM和炎症需要中的作用。我们的研究结果提供了一种新的机制，通过该机制 E ₂调节免疫系统，以及更年期如何导致骨质疏松症。低度炎症可能导致或促成绝经后观察到的其他合并症。© 2020 美国骨与矿物研究学会。