ArticleProceedings of the National Academy of Sciences of the United States of America2012
Nuclear receptor Nr4a1 modulates both regulatory T-cell (Treg) differentiation and clonal deletion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 128 citations in OpenAlex.
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- Immune-mediated Engagement of T Regulatory Cells with Tumor Cells Results in Trogocytosis and Tumor Cell Killing.bioRxiv : the preprint server for biology · 2025Article
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- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Inferring gene regulatory networks from single-cell multiome data using atlas-scale external data.Nature biotechnology · 2025Article
- Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.Nature communications · 2025Article
- Nuclear receptor 4A1 is critical for neutrophil-dependent pulmonary immunity toFrontiers in immunology · 2025Article
- A pan-family screen of nuclear receptors in immunocytes reveals ligand-dependent inflammasome control.Immunity · 2024Article
- The partitioning of TCR repertoires by thymic selection.The Journal of experimental medicine · 2024Review
- Tregs delivered post-myocardial infarction adopt an injury-specific phenotype promoting cardiac repair via macrophages in mice.Nature communications · 2024Article
- Targeting the TNF/IAP pathway synergizes with anti-CD3 immunotherapy in T-cell acute lymphoblastic leukemia.Blood · 2024Article
- PROTAC-mediated NR4A1 degradation as a novel strategy for cancer immunotherapy.The Journal of experimental medicine · 2024Article
- Exploring effects of gut microbiota on tertiary lymphoid structure formation for tumor immunotherapy.Frontiers in immunology · 2024Review
- Interleukin-17 directly stimulates tumor infiltrating Tregs to prevent cancer development.Frontiers in immunology · 2024Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Immature thymocytes expressing autoreactive T-cell receptors (TCR) can adopt differing cell fates: clonal deletion by apoptosis or deviation into alternative lineages such as FoxP3(+) regulatory T cells (Treg). We revisited the role of the transcription factor Nr4a1 (Nur77), an immediate-early response gene induced by TCR engagement. Nr4a1KO mice show clear quantitative defects in antigen-induced clonal deletion. The impact of the Nr4a1 deletion is not enhanced by deletion of the proapoptotic factor Bim. In addition, Nr4a1 curtails initial differentiation into the Treg lineage in TCR transgenic mice and in nontransgenic mice. Transcriptional profiling of Nr4a1KO thymocytes under selection conditions reveals that Nr4a1 activates the transcription of several targets, consistent with these diverse actions: (i) Nr4a1 partakes in the induction of Bim after TCR triggering; (ii) perhaps paradoxically, Nr4a1 positively controls several transcripts of the Treg signature, in particular Ikzf2 and Tnfrsf9; (iii) consistent with its prosurvival and metabolic role in the liver, Nr4a1 is also required for the induction by TCR of a coordinated set of enzymes of the glycolytic and Krebs cycle pathways, which we propose may antagonize Treg selection as does activation of mTOR/Akt. Thus, Nr4a1 appears to act as a balancing molecule in fate determination at a critical juncture of T-cell differentiation.
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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.