T reg deficiency‐mediated T H 1 response causes human premature ovarian insufficiency through apoptosis and steroidogenesis dysfunction of granulosa cells

作者：Xue Jiao, Xiruo Zhang, Nianyu Li, Dunfang Zhang, Shidou Zhao, Yujie Dang, Peter Zanvit, Wenwen Jin, Zi‐Jiang Chen, Wanjun Chen, Yingying Qin · 发表于：Clinical and Translational Medicine · 年份：2021 · DOI：10.1002/ctm2.448 · 被引用次数：98 · 研究领域：Reproductive System and Pregnancy、Reproductive Physiology in Livestock、Endometriosis Research and Treatment

Abstract 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 H 1) responses and regulatory T (T reg ) cell deficiency in both the periphery and the ovary compared to the control women. The increased ratio of T H 1:T reg cells was strongly correlated with the severity of POI. In mouse models of POI, the increased infiltration of T H 1 cells in the ovary resulted in follicle atresia and ovarian insufficiency, which could be prevented and reversed by T reg 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 reg cell deficiency‐mediated T H 1 response in the pathogenesis of POI, which should have implications for therapeutic interventions in patients with POI.