ArticleJCI insight2021
Estradiol resolves pneumonia via ERβ in regulatory T cells.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Trends and mortality due to acute respiratory distress syndrome in the United States (1999-2023): A 25-year nationwide study.Medicine · 2026Article
- CD4Nature communications · 2026Article
- Sex differences in immune responses to viruses, bacteria and vaccines.Nature immunology · 2026Review
- 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
- Interaction between the breast tumor microenvironment and gut microbiome.Gut microbes · 2025Review
- Addressing Sex as a Biological Variable in Preclinical Models of Lung Disease: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2025Article
- Sex Differences in Immune Responses to Infectious Diseases: The Role of Genetics, Hormones, and Aging.Diseases (Basel, Switzerland) · 2025Review
- Development of a preclinical model of ICU-associated sleep fragmentation and effects on pneumonia recovery in mice.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- The role of sex and gender in acute kidney injury-consensus statements from the 33rd Acute Disease Quality Initiative.Kidney international · 2025Article
- Sex-based difference in immune responses and efficacy of the pneumococcal conjugate vaccine.Journal of leukocyte biology · 2024Article
- The conneXion between sex and immune responses.Nature reviews. Immunology · 2024Review
- Sex differences in immune protection in mice conferred by heterologous vaccines for pneumonic plague.Frontiers in immunology · 2024Article
- Regulatory T cells in lung disease and transplantation.Bioscience reports · 2023Review
- Differential roles of regulatory T cells in acute respiratory infections.The Journal of clinical investigation · 2023Review
- Steady-state estradiol triggers a unique innate immune response to allergen resulting in increased airway resistance.Biology of sex differences · 2023Article
- Sex chromosome complement and sex steroid signaling underlie sex differences in immunity to respiratory virus infection.Frontiers in pharmacology · 2023Review
- Sex and Gender Differences in Bacterial Infections.Infection and immunity · 2022Review
- Article
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 1 institution in 1 country.
Funding
Abstract
Current treatments for pneumonia (PNA) are focused on the pathogens. Mortality from PNA-induced acute lung injury (PNA-ALI) remains high, underscoring the need for additional therapeutic targets. Clinical and experimental evidence exists for potential sex differences in PNA survival, with males having higher mortality. In a model of severe pneumococcal PNA, when compared with male mice, age-matched female mice exhibited enhanced resolution characterized by decreased alveolar and lung inflammation and increased numbers of Tregs. Recognizing the critical role of Tregs in lung injury resolution, we evaluated whether improved outcomes in female mice were due to estradiol (E2) effects on Treg biology. E2 promoted a Treg-suppressive phenotype in vitro and resolution of PNA in vivo. Systemic rescue administration of E2 promoted resolution of PNA in male mice independent of lung bacterial clearance. E2 augmented Treg expression of Foxp3, CD25, and GATA3, an effect that required ERβ, and not ERα, signaling. Importantly, the in vivo therapeutic effects of E2 were lost in Treg-depleted mice (Foxp3DTR mice). Adoptive transfer of ex vivo E2-treated Tregs rescued Streptococcus pneumoniae-induce PNA-ALI, a salutary effect that required Treg ERβ expression. E2/ERβ was required for Tregs to control macrophage proinflammatory responses. Our findings support the therapeutic role for E2 in promoting resolution of lung inflammation after PNA via ERβ Tregs.
Indexed as
Identifiers
What OpenQuestion holds
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.