ArticleThe Journal of experimental medicine2021
Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 12 citations in OpenAlex.
- Rag1-based time-stamp tracing of T-cell developmental origins.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- T cell receptor signaling induces expression of lysine demethylase KDM6B to maintain Treg homeostasis.The Journal of clinical investigation · 2026Article
- Control of naive T cell reactivity and peripheral tolerance by ascorbate and TET activity.Science advances · 2026Article
- Regulatory T cells in bullous pemphigoid: biological characteristics, dysfunction, and pathogenic roles.Frontiers in immunology · 2026Review
- Thirty years in, regulatory T cells are ready for medicine.Frontiers in immunology · 2026Review
- The relativity of regulatory T cell suppression modes.Frontiers in immunology · 2026Review
- Regulatory T Cell-Based Adoptive Cell Therapy in Autoimmunity.International journal of molecular sciences · 2025Review
- Constructing a Pan-Cancer Prognostic Model via Machine Learning Based on Immunogenic Cell Death Genes and Identifying NT5E as a Biomarker in Head and Neck Cancer.Current issues in molecular biology · 2025Article
- Pharmacological mechanisms of traditional Chinese medicine metabolites in regulating Treg cells: an integrative pathway review.Frontiers in pharmacology · 2025Review
- Dynamic Foxp3-chromatin interaction controls tunable Treg cell function.The Journal of experimental medicine · 2024Article
- Regulatory T Cells for Control of Autoimmunity.Advances in experimental medicine and biology · 2024Article
- Elusive modes of Foxp3 activity in versatile regulatory T cells.Frontiers in immunology · 2024Review
- Genomic Analysis of Foxp3 Function in Regulatory T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- DNA Methylation in Regulatory T Cell Differentiation and Function: Challenges and Opportunities.Biomolecules · 2022Review
- Nature vs. nurture: FOXP3, genetics, and tissue environment shape Treg function.Frontiers in immunology · 2022Review
- Control of Foxp3 induction and maintenance by sequential histone acetylation and DNA demethylation.Cell reports · 2021Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
T reg cells bearing a diverse antigen receptor repertoire suppress pathogenic T cells and maintain immune homeostasis during their long lifespan. How their robust function is determined genetically remains elusive. Here, we investigate the regulatory space of the cis-regulatory elements of T reg lineage-specifying factor Foxp3. Foxp3 enhancers are known as distinct readers of environmental cues controlling T reg cell induction or lineage stability. However, their single deficiencies cause mild, if any, immune dysregulation, leaving the key transcriptional mechanisms determining Foxp3 expression and thereby T reg cell suppressive capacity uncertain. We examined the collective activities of Foxp3 enhancers and found that they coordinate to maximize T reg cell induction, Foxp3 expression level, or lineage stability through distinct modes and that ablation of synergistic enhancers leads to lethal autoimmunity in young mice. Thus, the induction and maintenance of a diverse, stable T reg cell repertoire rely on combinatorial Foxp3 enhancers, suggesting broad, stage-specific, synergistic activities of cell-intrinsic factors and cell-extrinsic cues in determining T reg cell suppressive capacity.
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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.