ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Estradiol inhibits Th17 cell differentiation through inhibition of RORγT transcription by recruiting the ERα/REA complex to estrogen response elements of the RORγT promoter.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Sex hormones affect the pathogenesis and clinical characteristics of systemic lupus erythematosus.Frontiers in medicine · 2022Pooled it
- Sex steroids and autoimmune rheumatic diseases: state of the art.Nature reviews. Rheumatology · 2020Pooled it
- Associations between improvement in genitourinary symptoms of menopause and changes in the vaginal ecosystem.Menopause (New York, N.Y.) · 2018Trial
- Sex-Biased Immunity: The Hidden Variable in Immuno-oncology.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Role of sex and gender in autoimmune thyroid diseases: mechanisms and knowledge gaps.Reviews in endocrine & metabolic disorders · 2026Review
- Sex Steroid Hormone Regulation of T-Cell Function and Antitumor Immunity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Association between sex hormones and innate cytotoxic capacity of circulating and rectal mucosal immune cells.Clinical immunology communications · 2026Article
- Unveiling estrogen's role: a comprehensive review of its impact on skin health and disease.Apoptosis : an international journal on programmed cell death · 2026Review
- Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha.Nature communications · 2025Article
- The Effect of Estradiol and Testosterone Levels Alone or in Combination with Their Receptors in Predicting the Severity of Systemic Lupus Erythematosus: A Cohort Study.Iranian journal of medical sciences · 2025Article
- Preexisting vaccine-primed heterosubtypic T cell immunity protects the maternal-fetal unit from adverse influenza outcomes in mice.The Journal of clinical investigation · 2025Article
- Multi-omics analysis identified macrophages as key contributors to sex-related differences in ulcerative colitis.Frontiers in immunology · 2025Article
- Article
- HIV-1 latency reversal and immune enhancing activity of IL-15 is not influenced by sex hormones.JCI insight · 2024Article
- Function and expression of N-acetyltransferases 1 and 2 are altered in lymphocytes in type 2 diabetes and obesity.Biochemistry and biophysics reports · 2024Article
- Specific and shared biological functions of PARP2 - is PARP2 really a lil' brother of PARP1?Expert reviews in molecular medicine · 2024Review
- Hallmarks of sex bias in immuno-oncology: mechanisms and therapeutic implications.Nature reviews. Cancer · 2024Article
- The potential application of fermented tea as a drink for regulating bone mass.Frontiers in pharmacology · 2024Review
- Association between gut microbiota and menstrual disorders: a two-sample Mendelian randomization study.Frontiers in microbiology · 2024Article
- Sex-Related Effect of Aging in Gingival Gamma-Delta T Cells.Journal of dental research · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The symptoms of vaginal candidiasis exacerbate in the second half of the menstrual cycle in premenopausal women when the serum estradiol level is elevated. Estradiol has been shown to inhibit Th17 differentiation and production of antifungal IL-17 cytokines. However, little is known about the mechanisms. In the present study, we used mouse splenocytes and found that estradiol inhibited Th17 differentiation through downregulation of Rorγt mRNA and protein expression. Estradiol activated estrogen receptor (ER)α to recruit repressor of estrogen receptor activity (REA) and form the ERα/REA complex. This complex bound to three estrogen response element (ERE) half-sites on the Rorγt promoter region to suppress Rorγt expression. Estradiol induced Rea mRNA and protein expression in mouse splenocytes. Using Rea small interfering RNA to knock down Rea expression enhanced Rorγt expression and Th17 differentiation. Alternatively, histone deacetylase 1 and 2 bound to the three ERE half-sites, independent of estradiol. Histone deacetylase inhibitor MS-275 dose- and time-dependently increased Rorγt expression and subsequently enhanced Th17 differentiation. In 15 healthy premenopausal women, high serum estradiol levels are correlated with low RORγT mRNA levels and high REA mRNA levels in the vaginal lavage. These results demonstrate that estradiol upregulates REA expression and recruits REA via ERα to the EREs on the RORγT promoter region, thus inhibiting RORγT expression and Th17 differentiation. This study suggests that the estradiol/ERα/REA axis may be a feasible target in the management of recurrent vaginal candidiasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.