ArticlePLoS pathogens2017
Progesterone impairs antigen-non-specific immune protection by CD8 T memory cells via interferon-γ gene hypermethylation.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- A Systematic Review and Meta-analysis of the Adverse Effects of Levonorgestrel Emergency Oral Contraceptive.Clinical drug investigation · 2020Pooled it
- Trypanosoma brucei infection remodels the uterine immune environment and drives neuroendocrine dysfunction.PLoS pathogens · 2026Article
- The HIV Reservoir and Immune Landscape Across the Life Course of Women: Implications for Cure Strategies.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- Immune modulation by sex hormones: unveiling the complex interplay and regulatory networks.Frontiers in immunology · 2026Review
- Hallmarks of sex bias in immuno-oncology: mechanisms and therapeutic implications.Nature reviews. Cancer · 2024Article
- Apolipoprotein E genotype affects innate susceptibility toInfection and immunity · 2023Article
- Regulatory T cells are paramount effectors in progesterone regulation of embryo implantation and fetal growth.JCI insight · 2023Article
- Animal Models for Studying Congenital Transmission of Hepatitis E Virus.Microorganisms · 2023Review
- Sex and Gender Differences in Bacterial Infections.Infection and immunity · 2022Review
- Article
- Spotlight on the Gut Microbiome in Menopause: Current Insights.International journal of women's health · 2022Review
- DNA Methylation and Immune Memory Response.Cells · 2021Review
- Progesterone promotes immunomodulation and tumor development in the murine mammary gland.Journal for immunotherapy of cancer · 2021Article
- Direct and Indirect endocrine-mediated suppression of human endometrial CD8+T cell cytotoxicity.Scientific reports · 2021Article
- The impact of 17β-estradiol and progesterone therapy on peripheral blood mononuclear cells of asthmatic patients.Molecular biology reports · 2021Article
- Progesterone Dampens Immune Responses inFrontiers in immunology · 2021Article
- Progesterone-Related Immune Modulation of Pregnancy and Labor.Frontiers in endocrinology · 2019Review
- Progesterone Modulation of Pregnancy-Related Immune Responses.Frontiers in immunology · 2018Article
- The Wonder Years: What Can Primary School Children Teach Us About Immunity toFrontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pregnant women and animals have increased susceptibility to a variety of intracellular pathogens including Listeria monocytogenes (LM), which has been associated with significantly increased level of sex hormones such as progesterone. CD8 T memory(Tm) cell-mediated antigen-non-specific IFN-γ responses are critically required in the host defense against LM. However, whether and how increased progesterone during pregnancy modulates CD8 Tm cell-mediated antigen-non-specific IFN-γ production and immune protection against LM remain poorly understood. Here we show in pregnant women that increased serum progesterone levels are associated with DNA hypermethylation of IFN-γ gene promoter region and decreased IFN-γ production in CD8 Tm cells upon antigen-non-specific stimulation ex vivo. Moreover, IFN-γ gene hypermethylation and significantly reduced IFN-γ production post LM infection in antigen-non-specific CD8 Tm cells are also observed in pregnant mice or progesterone treated non-pregnant female mice, which is a reversible phenotype following demethylation treatment. Importantly, antigen-non-specific CD8 Tm cells from progesterone treated mice have impaired anti-LM protection when adoptive transferred in either pregnant wild type mice or IFN-γ-deficient mice, and demethylation treatment rescues the adoptive protection of such CD8 Tm cells. These data demonstrate that increased progesterone impairs immune protective functions of antigen-non-specific CD8 Tm cells via inducing IFN-γ gene hypermethylation. Our findings thus provide insights into a new mechanism through which increased female sex hormone regulate CD8 Tm cell functions during pregnancy.
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