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T reg deficiency‐mediated T H 1 response causes human premature ovarian insufficiency through apoptosis and steroidogenesis dysfunction of granulosa cells
- Source :
- Clinical and Translational Medicine, Clinical and Translational Medicine, Vol 11, Iss 6, Pp n/a-n/a (2021)
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
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.<br />The Treg cells deficiency with decreased number and impaired suppression function mediate augmented TH1 responses in premature ovarian insufficiency (POI). The increased TH1 proinflammatory cytokines IFN‐γ and TNF‐α impair steroidogenesis by targeting CYP19A1 and promote apoptosis of granulosa cells partially by down‐regulation of CTGF via JAK‐STAT1 and NF‐κB activation, hence contribute to follicle atresia, ovarian dysfunction and premature insufficiency.
- Subjects :
- Adult
0301 basic medicine
Medicine (General)
steroidogenesis
Cell
Medicine (miscellaneous)
Ovary
Primary Ovarian Insufficiency
Premature ovarian insufficiency
medicine.disease_cause
T-Lymphocytes, Regulatory
Interferon-gamma
Mice
03 medical and health sciences
R5-920
0302 clinical medicine
Interferon
medicine
Animals
Humans
Research Articles
Granulosa Cells
Tumor Necrosis Factor-alpha
business.industry
POI
apoptosis
Th1 Cells
Immune dysregulation
TH1
Mice, Inbred C57BL
CTGF
030104 developmental biology
medicine.anatomical_structure
Apoptosis
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Female
Steroids
Tumor necrosis factor alpha
business
Treg cells
Research Article
medicine.drug
Subjects
Details
- ISSN :
- 20011326
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Clinical and Translational Medicine
- Accession number :
- edsair.doi.dedup.....ca55db07a2b853de480113ef3682bc2d