ArticleProceedings of the National Academy of Sciences of the United States of America2020
Impaired estrogen signaling underlies regulatory T cell loss-of-function in the chronically inflamed intestine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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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
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Sex-Dimorphic Analyses Identify Novel and Sex-Specific Genetic Associations in Inflammatory Bowel Disease.Inflammatory bowel diseases · 2023Pooled it
- Gut dysbiosis, blood pressure regulation, and cardiometabolic risk in polyendocrine metabolic ovarian syndrome (PMOS).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
- An Estrogen-IL-33 Circuit in Aortic Fibroblasts Underlies Sex Differences in Tregs in Abdominal Aortic Aneurysm.JACC. Basic to translational science · 2026Article
- Pre-Treatment with Estradiol, But not Progesterone, Exacerbates DSS Colitis: Dysregulated Innate Immunity and Impaired Epithelial Damage Response.Inflammation · 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
- Glucocorticoid-induced Leucine Zipper (GILZ) is a novel secreted protein by intestinal L-cells and is dysregulated during active ulcerative colitis.Cell death discovery · 2026Article
- The Gut Microbiome in HIV Pathogenesis: Interconnections Between Dysbiosis, Immune Dysfunction, and Viral Persistence.International journal of molecular sciences · 2026Review
- The Gut-Muscle Axis in Sarcopenia: Mechanisms, Evidence Gaps and Translational Challenges.Biomedicines · 2026Review
- Sex differences in immune responses to viruses, bacteria and vaccines.Nature immunology · 2026Review
- Inhibition of estrogen receptor alpha stabilizes regulatory T cell function in autoimmune hepatitis.JHEP reports : innovation in hepatology · 2026Article
- Glucocorticoid-induced leucine zipper as a context-dependent central integrator of innate and adaptive immune homeostasis.Frontiers in immunology · 2026Review
- Decoding Barberry Root's Therapeutic Network: A Synergistic Solution for IBS-D.Combinatorial chemistry & high throughput screening · 2026Article
- Regulatory T cells in human pregnancy: mechanisms, dysregulation, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Sex differences in immune cells: mechanistic perspectives and clinical correlates in physiology and disease.Frontiers in immunology · 2026Review
- Sheep placental extract ameliorates polycystic ovary syndrome in rats by regulating ERβ-mediated Treg cells via the TGF-β1/Smad3 signaling pathway.Frontiers in immunology · 2026Article
- Influence of biological sex in inflammatory bowel diseases.Nature reviews. Gastroenterology & hepatology · 2025Review
- Estrogen Receptor Alpha Contributes to Intestinal Inflammation in a Murine Model of Ileitis.Journal of cellular immunology · 2025Article
- Sex Differences in Colonic Inflammation are Driven by Epithelial-Specific Expression of Estrogen Receptor Alpha.Gastro hep advances · 2025Article
- Sex bias in tumor immunity: insights from immune cells.Theranostics · 2025Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Signaling of 17β-estradiol (estrogen) through its two nuclear receptors, α and β (ERα, ERβ), is an important mechanism of transcriptional regulation. Although ERs are broadly expressed by cells of the immune system, the mechanisms by which they modulate immune responses remain poorly understood. ERβ-specific signaling is reduced in patients with chronic inflammatory diseases, including systemic lupus erythematosus and inflammatory bowel disease, and our previous work suggests that dysregulation of ERβ-specific signaling contributes to enhanced intestinal inflammation in female SAMP/YitFC mice, a spontaneous model of Crohn's disease-like ileitis. The present study builds on these prior observations to identify a nonredundant, immunoprotective role for ERβ-specific signaling in TGF-β-dependent regulatory T cell (Treg) differentiation. Using a strain of congenic SAMP mice engineered to lack global expression of ERβ, we observed dramatic, female-specific exacerbation of intestinal inflammation accompanied by significant reductions in intestinal Treg frequency and function. Impaired Treg suppression in the absence of ERβ was associated with aberrant overexpression of
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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.