ArticlePLoS pathogens2016
Estradiol Enhances CD4+ T-Cell Anti-Viral Immunity by Priming Vaginal DCs to Induce Th17 Responses via an IL-1-Dependent Pathway.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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.
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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
45 citing papers in PubMed, 55 citations in OpenAlex.
- An IL-1, IL-17, and IL-22 cytokine circuit controls vulvovaginal candidiasis independently of estrogen.PLoS pathogens · 2026Article
- The effect of estrogen and its receptors on the progression of cervical intraepithelial neoplasia in postmenopausal women through synergistic interaction with HPV.BMC women's health · 2026Article
- Balancing Host Defense and Viral Tolerance for the Development of Next-Generation Broad-Spectrum Antiviral Agents.Pathogens (Basel, Switzerland) · 2025Review
- Estradiol enhances B cell humoral immune responses against genital herpes simplex virus type 2 in mice through an IL-17 dependant pathway.Frontiers in immunology · 2025Article
- Impact of Psychological Stress-Derived Hormones and Cytokines on Immune Cell Profiles in Vitiligo: Toward Improved Peripheral Blood Simulation in Animal Models.Clinical, cosmetic and investigational dermatology · 2025Review
- Infertility, IL-17, IL-33 and Microbiome Cross-Talk: The Extended ARIA-MeDALL Hypothesis.International journal of molecular sciences · 2024Review
- Vaccine-elicited IL-1R signaling results in Th17 TRM-mediated immunity.Communications biology · 2024Article
- NET-EN treatment leads to delayed HSV-2 infection, enhanced mucin and T cell functions in the female genital tract when compared to DMPA in a preclinical mouse model.Frontiers in immunology · 2024Article
- Phytoestrogen-Based Hormonal Replacement Therapy Could Benefit Women Suffering Late-Onset Asthma.International journal of molecular sciences · 2023Review
- Microbial Components and Effector Molecules in T Helper Cell Differentiation and Function.Immune network · 2023Review
- The Double Game Played by Th17 Cells in Infection: Host Defense and Immunopathology.Pathogens (Basel, Switzerland) · 2022Review
- Network Pharmacology and Molecular Docking Analysis Reveal Insights into the Molecular Mechanism of Shengma-Gegen Decoction on Monkeypox.Pathogens (Basel, Switzerland) · 2022Article
- Regulatory Roles of Estrogens in Psoriasis.Journal of clinical medicine · 2022Review
- Role of hormones in the pregnancy and sex-specific outcomes to infections with respiratory viruses.Immunological reviews · 2022Review
- Systemic Neutralizing Antibodies and Local Immune Responses Are Critical for the Control of SARS-CoV-2.Viruses · 2022Article
- Article
- Effect of Female Sex Hormones on the Immune Response againstPathogens (Basel, Switzerland) · 2022Article
- The Role of IL-17 During Infections in the Female Reproductive Tract.Frontiers in immunology · 2022Review
- Th17 cell differentiation induced by cytopathogenic biotype BVDV-2 in bovine PBLCs.BMC genomics · 2021Article
- Vaginal delivery of vaccines.Advanced drug delivery reviews · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
Clinical and experimental studies have shown that estradiol (E2) confers protection against HIV and other sexually transmitted infections. Here, we investigated the underlying mechanism. Better protection in E2-treated mice, immunized against genital HSV-2, coincided with earlier recruitment and higher proportions of Th1 and Th17 effector cells in the vagina post-challenge, compared to placebo-treated controls. Vaginal APCs isolated from E2-treated mice induced 10-fold higher Th17 and Th1 responses, compared to APCs from progesterone-treated, placebo-treated, and estradiol-receptor knockout mice in APC-T cell co-cultures. CD11c+ DCs in the vagina were the predominant APC population responsible for priming these Th17 responses, and a potent source of IL-6 and IL-1β, important factors for Th17 differentiation. Th17 responses were abrogated in APC-T cell co-cultures containing IL-1β KO, but not IL-6 KO vaginal DCs, showing that IL-1β is a critical factor for Th17 induction in the genital tract. E2 treatment in vivo directly induced high expression of IL-1β in vaginal DCs, and addition of IL-1β restored Th17 induction by IL-1β KO APCs in co-cultures. Finally, we examined the role of IL-17 in anti-HSV-2 memory T cell responses. IL-17 KO mice were more susceptible to intravaginal HSV-2 challenge, compared to WT controls, and vaginal DCs from these mice were defective at priming efficient Th1 responses in vitro, indicating that IL-17 is important for the generation of efficient anti-viral memory responses. We conclude that the genital mucosa has a unique microenvironment whereby E2 enhances CD4+ T cell anti-viral immunity by priming vaginal DCs to induce Th17 responses through an IL-1-dependent pathway.
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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.