Treg deficiency‐mediated TH1 response causes human premature ovarian insufficiency through apoptosis and steroidogenesis dysfunction of granulosa cells

Autor: Xue Jiao, Xiruo Zhang, Nianyu Li, Dunfang Zhang, Shidou Zhao, Yujie Dang, Peter Zanvit, Wenwen Jin, Zi‐Jiang Chen, Wanjun Chen, Yingying Qin
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Clinical and Translational Medicine, Vol 11, Iss 6, Pp n/a-n/a (2021)
Druh dokumentu: article
ISSN: 2001-1326
DOI: 10.1002/ctm2.448
Popis: 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 (TH1) responses and regulatory T (Treg) cell deficiency in both the periphery and the ovary compared to the control women. The increased ratio of TH1:Treg cells was strongly correlated with the severity of POI. In mouse models of POI, the increased infiltration of TH1 cells in the ovary resulted in follicle atresia and ovarian insufficiency, which could be prevented and reversed by Treg 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 Treg cell deficiency‐mediated TH1 response in the pathogenesis of POI, which should have implications for therapeutic interventions in patients with POI.
Databáze: Directory of Open Access Journals