ArticleCell2012
Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict.
Article in Cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 341 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
341 citing papers in PubMed, 2 syntheses or guidelines pooled it, 604 citations in OpenAlex.
- Tamoxifen and Fertility in Women with Breast Cancer: A Systematic Review on Reproductive Outcomes and Oncological Safety of Treatment Interruption.International journal of molecular sciences · 2025Pooled it
- Crosstalk Between Trophoblasts and Decidual Immune Cells: The Cornerstone of Maternal-Fetal Immunotolerance.Frontiers in immunology · 2021Pooled it
- Effector and Activated T Cells Induce Preterm Labor and Birth That Is Prevented by Treatment with Progesterone.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- Clonally Expanded Decidual Effector Regulatory T Cells Increase in Late Gestation of Normal Pregnancy, but Not in Preeclampsia, in Humans.Frontiers in immunology · 2018Trial
- Proteomic Insights Into Human Induced Regulatory T Cells: The Role of LPXN and CD160 in Immune Suppression.Molecular & cellular proteomics : MCP · 2026Article
- Microchimerism: The Hidden Cellular Dialogue Between Mother and Fetal That Shapes Lifelong Immunity.Expert reviews in molecular medicine · 2026Review
- Short-Chain Fatty Acids May Promote Regulatory T Cell Induction to Enhance Maternal Immune Tolerance in Early Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- From Tregs to tissue remodelling: FOXP3 and IL-35 in the inflammatory landscape of nasal polyps.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Article
- CNS1-dependent regulatory T cells shape recovery from acute lung injury.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Immune Imbalance in Sickle Cell Anemia: Flow Cytometric Insights Into Regulatory T Cells and Neutrophil Dynamics.Journal of clinical laboratory analysis · 2026Article
- Review
- The molecular evolution of vertebrate organs.Nature ecology & evolution · 2026Review
- Maternal Krüppel-like factor 2 (KLF2)+ CD4 T cells promote fertility and fetal tolerance.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Immune cellular homeostasis and its breakdown at the maternal-fetal interface.Trends in immunology · 2026Review
- Review
- Article
- Immune dysregulation linking pre-pregnancy obesity to gestational diabetes mellitus.Frontiers in immunology · 2026Review
- Defining nature, responses and drivers of regulatory- and conventional CD4Frontiers in immunology · 2026Article
- Regulatory T cells in human pregnancy: mechanisms, dysregulation, and therapeutic perspectives.Frontiers in immunology · 2026Review
281 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Regulatory T (Treg) cells, whose differentiation and function are controlled by X chromosome-encoded transcription factor Foxp3, are generated in the thymus (tTreg) and extrathymically (peripheral, pTreg), and their deficiency results in fatal autoimmunity. Here, we demonstrate that a Foxp3 enhancer, conserved noncoding sequence 1 (CNS1), essential for pTreg but dispensable for tTreg cell generation, is present only in placental mammals. CNS1 is largely composed of mammalian-wide interspersed repeats (MIR) that have undergone retrotransposition during early mammalian radiation. During pregnancy, pTreg cells specific to a model paternal alloantigen were generated in a CNS1-dependent manner and accumulated in the placenta. Furthermore, when mated with allogeneic, but not syngeneic, males, CNS1-deficient females showed increased fetal resorption accompanied by increased immune cell infiltration and defective remodeling of spiral arteries. Our results suggest that, during evolution, a CNS1-dependent mechanism of extrathymic differentiation of Treg cells emerged in placental animals to enforce maternal-fetal tolerance.
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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.