ArticleThe Journal of experimental medicine2014
Dynamic changes in E-protein activity regulate T reg cell development.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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.
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- Id3 expression identifies CD4Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The E-Id Axis Instructs Adaptive Versus Innate Lineage Cell Fate Choice and Instructs Regulatory T Cell Differentiation.Frontiers in immunology · 2022Review
- Ubiquitin Specific Protease 1 Expression and Function in T Cell Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Transcriptional regulation of Treg homeostasis and functional specification.Cellular and molecular life sciences : CMLS · 2020Review
- The Transcriptional Regulator Id2 Is Critical for Adipose-Resident Regulatory T Cell Differentiation, Survival, and Function.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- E-protein regulatory network links TCR signaling to effector Treg cell differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation.Nature immunology · 2016Article
- T cell receptor signalling in the control of regulatory T cell differentiation and function.Nature reviews. Immunology · 2016Review
- Rapid cloning, expression, and functional characterization of paired αβ and γδ T-cell receptor chains from single-cell analysis.Molecular therapy. Methods & clinical development · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
E-proteins are TCR-sensitive transcription factors essential for intrathymic T cell transitions. Here, we show that deletion of E-proteins leads to both enhanced peripheral TGF-β-induced regulatory T (iT reg) cell and thymic naturally arising T reg cell (nT reg cell) differentiation. In contrast, deletion of Id proteins results in reduced nT reg cell differentiation. Mechanistic analysis indicated that decreased E-protein activity leads to de-repression of signaling pathways that are essential to Foxp3 expression. Decreased E-protein binding to an IL-2Rα enhancer locus facilitated TCR-induced IL-2Rα expression. Similarly, decreased E-protein activity facilitated TCR-induced NF-κB activation and generation of c-Rel. Consistent with this, microarray analysis indicated that cells with E-protein depletion that are not yet expressing Foxp3 exhibit activation of the IL-2 and NF-κB signaling pathways as well as enhanced expression of many of the genes associated with Foxp3 induction. Finally, studies using Nur77-GFP mice to monitor TCR signaling showed that TCR signaling strength sufficient to induce Foxp3 differentiation is accompanied by down-regulation of E-protein levels. Collectively, these data suggest that TCR stimulation acts in part through down-regulation of E-protein activity to induce T reg cell lineage development.
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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.