ArticleImmunity2013
Foxp3 transcription factor is proapoptotic and lethal to developing regulatory T cells unless counterbalanced by cytokine survival signals.
Article in Immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
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Who cites it
144 citing papers in PubMed, 216 citations in OpenAlex.
- TCR signal strength during positive selection shapes CD25 expression patterns on thymically derived regulatory T cells.bioRxiv : the preprint server for biology · 2026Article
- Limited roles of the miR-17-92 cluster in the regulation of T-cell apoptosis.The FEBS journal · 2026Article
- From Development to Aging: Dynamic Roles of the Thymic Medulla in T Cell Biology.Immunological reviews · 2026Review
- Ripk1 is critical for preserving effector regulatory T cells and the suppressive transcriptional program in regulatory T cells.Cell death and differentiation · 2026Article
- Targeting DAP5 Disrupts Alternate Mode of Translational Initiation in Tregs and Potentiates Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TET2: a critical regulatory hub with broad therapeutic implications across human diseases.Frontiers in immunology · 2026Review
- [Guardians of Immune Tolerance: Regulatory T Cells].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Review
- A linear ontogeny accounts for the development of naive, memory, and tumor-infiltrating regulatory T cells in mice.Science immunology · 2025Article
- Nuclear receptor corepressor 1 controls regulatory T cell subset differentiation and effector function.eLife · 2024Article
- Lymphotoxin limits Foxp3Nature communications · 2024Article
- Article
- Interleukin-2 signaling in the regulation of T cell biology in autoimmunity and cancer.Immunity · 2024Review
- New insights into developmental fate decisions by autoreactive CD4 thymocytes.Clinical and translational medicine · 2024Article
- A guide to thymic selection of T cells.Nature reviews. Immunology · 2024Review
- Mechanism study of ubiquitination in T cell development and autoimmune disease.Frontiers in immunology · 2024Review
- Neuroimmune cell interactions and chronic infections in oral cancers.Frontiers in medicine · 2024Article
- Regulatory T Cells for Control of Autoimmunity.Advances in experimental medicine and biology · 2024Article
- Oxidized Phospholipid oxPAPC Alters Regulatory T-Cell Differentiation and Decreases Their Protective Function in Atherosclerosis in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- An essential role for miR-15/16 in Treg suppression and restriction of proliferation.Cell reports · 2023Article
- Systems immunology of regulatory T cells: can one circuit explain it all?Trends in immunology · 2023Review
84 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Immune tolerance requires regulatory T (Treg) cells to prevent autoimmune disease, with the transcription factor Foxp3 functioning as the critical regulator of Treg cell development and function. We report here that Foxp3 was lethal to developing Treg cells in the thymus because it induced a unique proapoptotic protein signature (Puma⁺⁺⁺p-Bim⁺⁺p-JNK⁺⁺DUSP6⁻) and repressed expression of prosurvival Bcl-2 molecules. However, Foxp3 lethality was prevented by common gamma chain (γc)-dependent cytokine signals that were present in the thymus in limiting amounts sufficient to support only ∼1 million Treg cells. Consequently, most newly arising Treg cells in the thymus were deprived of this signal and underwent Foxp3-induced death, with Foxp3⁺CD25⁻ Treg precursor cells being the most susceptible. Thus, we identify Foxp3 as a proapoptotic protein that requires developing Treg cells to compete with one another for limiting amounts of γc-dependent survival signals in the thymus.
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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.