ArticleMolecular and cellular biology2014
Tle4 regulates epigenetic silencing of gamma interferon expression during effector T helper cell tolerance.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Epigenome-wide association study of psilocybin-induced methylome changes in alcohol use disorder.Translational psychiatry · 2026Trial
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Profiling Genome-Wide Methylation Patterns in Cattle Infected withInternational journal of molecular sciences · 2024Article
- Explainable machine learning identifies multi-omics signatures of muscle response to spaceflight in mice.NPJ microgravity · 2023Article
- Tle4 controls both developmental acquisition and early post-natal maturation of corticothalamic projection neuron identity.Cell reports · 2023Article
- Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation.Frontiers in cell and developmental biology · 2022Review
- Gene editing to enhance the efficacy of cancer cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- CRISPR Screening of CAR T Cells and Cancer Stem Cells Reveals Critical Dependencies for Cell-Based Therapies.Cancer discovery · 2021Article
- The Notch signaling pathway involvement in innate lymphoid cell biology.Biomedical journal · 2021Review
- Article
- The ER membrane-anchored ubiquitin ligase Hrd1 is a positive regulator of T-cell immunity.Nature communications · 2016Article
- The heterogeneity of human CD127(+) innate lymphoid cells revealed by single-cell RNA sequencing.Nature immunology · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In response to suboptimal activation, T cells become hyporesponsive, with a severely reduced capacity to proliferate and produce cytokines upon reencounter with antigen. Chromatin analysis of T cells made tolerant by use of different in vitro and in vivo approaches reveals that the expression of gamma interferon (IFN-γ) is epigenetically silenced in anergic effector TH1 cells. In those T cells, calcium signaling triggers the expression of Tle4, a member of the Groucho family of corepressors, which is then recruited to a distal regulatory element in the Ifng locus and causes the establishment of repressive epigenetic marks at the Ifng gene regulatory elements. Consequently, impaired Tle4 activity results in a markedly reduced capacity to inhibit IFN-γ production in tolerized T cells. We propose that Blimp1-dependent recruitment of Tle4 to the Ifng locus causes epigenetic silencing of the expression of the Ifng gene in anergic TH1 cells. These results define a novel function of Groucho family corepressors in peripheral T cells and demonstrate that specific mechanisms are activated in tolerant T helper cells to directly repress expression of effector cytokines, supporting the hypothesis that stable epigenetic imprinting contributes to the maintenance of the tolerance-associated hyporesponsive phenotype in T cells.
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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.