Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Mucosal Immunology Section, NIDCR, National Institutes of Health, Bethesda, Maryland, USA.
Clin Transl Med. 2021 Jun;11(6):e448. doi: 10.1002/ctm2.448.
Immune dysregulation has long been proposed as a component of premature ovarian insufficiency (POI), but the underlying mediators and mechanisms remain largely unknown. Here we showed that patients with POI had augmented T helper 1 (T 1) responses and regulatory T (T ) cell deficiency in both the periphery and the ovary compared to the control women. The increased ratio of T 1:T cells was strongly correlated with the severity of POI. In mouse models of POI, the increased infiltration of T 1 cells in the ovary resulted in follicle atresia and ovarian insufficiency, which could be prevented and reversed by T cells. Importantly, interferon (IFN) -γ and tumor necrosis factor (TNF) -α cooperatively promoted the apoptosis of granulosa cells and suppressed their steroidogenesis by modulating CTGF and CYP19A1. We have thus revealed a previously unrecognized T cell deficiency-mediated T 1 response in the pathogenesis of POI, which should have implications for therapeutic interventions in patients with POI.
免疫失调早已被认为是卵巢早衰 (POI) 的一个组成部分，但潜在的介质和机制在很大程度上仍然未知。在这里，我们发现与对照组女性相比，POI 患者的外周血和卵巢中辅助性 T 细胞 1 (T 1) 反应增强，调节性 T (Treg) 细胞缺失。T 1:T 细胞比值的增加与 POI 的严重程度密切相关。在 POI 的小鼠模型中，卵巢中 T 1 细胞的浸润增加导致卵泡闭锁和卵巢功能不全，而 T 细胞可以预防和逆转这种情况。重要的是，干扰素 (IFN)-γ 和肿瘤坏死因子 (TNF)-α 通过调节 CTGF 和 CYP19A1 协同促进颗粒细胞凋亡并抑制其类固醇生成。因此，我们揭示了 POI 发病机制中以前未被识别的 T 细胞缺陷介导的 T 1 反应，这对于 POI 患者的治疗干预应该具有重要意义。
