ArticleJCI insight2021
NR4A family members regulate T cell tolerance to preserve immune homeostasis and suppress autoimmunity.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- Proteomic Insights Into Human Induced Regulatory T Cells: The Role of LPXN and CD160 in Immune Suppression.Molecular & cellular proteomics : MCP · 2026Article
- Systems mapping of intra-donor, cross-tissue T cell clonal expansion and tissue adaptation in the gut-liver-blood axis.Cell reports · 2026Article
- The effect of walnut consumption on the peripheral blood mononuclear cell transcriptome.Genes & nutrition · 2026Article
- NR4A1 limits CD8Research square · 2026Article
- NR4A1 limits CD8⁺ T Cell effector responses and protection in tuberculosis.bioRxiv : the preprint server for biology · 2026Article
- Alleviation of experimental arthritis in SKG mice throughFrontiers in immunology · 2026Article
- Ocular immune privilege in action: The living eye imposes unique regulatory and anergic gene signatures on uveitogenic T cells.Cell reports · 2025Article
- The mechanisms and clinical significance of CD8Cancer biology & medicine · 2025Review
- 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
- Article
- Analysing the gene expression profiles of the orphan nuclear receptors NR4A1, NR4A2 and NR4A3 in premalignant lesions of the cervix and cervicitis.European journal of obstetrics & gynecology and reproductive biology: X · 2024Article
- The partitioning of TCR repertoires by thymic selection.The Journal of experimental medicine · 2024Review
- Infiltrating treg reprogramming in the tumor immune microenvironment and its optimization for immunotherapy.Biomarker research · 2024Review
- Elucidating immune-related gene transcriptional programs via factorization of large-scale RNA-profiles.iScience · 2024Article
- Comparative safety, pharmacokinetics, and off-target assessment of 1,1-bis(3'-indolyl)-1-(Toxicology research · 2024Article
- PROTAC-mediated NR4A1 degradation as a novel strategy for cancer immunotherapy.The Journal of experimental medicine · 2024Article
- Cbl-b mitigates the responsiveness of naive CD8Science signaling · 2024Article
- Transcriptional rewiring in CD8Frontiers in immunology · 2024Review
- The circadian clock gene BMAL1 modulates autoimmunity features in lupus.Frontiers in immunology · 2024Article
- Sex- and Female Age-Dependent Differences in Gene Expression in Diffuse Large B-Cell Lymphoma-Possible Estrogen Effects.Cancers · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The NR4A family of orphan nuclear receptors (Nr4a1-3) plays redundant roles to establish and maintain Treg identity; deletion of multiple family members in the thymus results in Treg deficiency and a severe inflammatory disease. Consequently, it has been challenging to unmask redundant functions of the NR4A family in other immune cells. Here we use a competitive bone marrow chimera strategy, coupled with conditional genetic tools, to rescue Treg homeostasis and unmask such functions. Unexpectedly, chimeras harboring Nr4a1-/- Nr4a3-/- (double-knockout, DKO) bone marrow developed autoantibodies and a systemic inflammatory disease despite a replete Treg compartment of largely WT origin. This disease differs qualitatively from that seen with Treg deficiency and is B cell extrinsic. Negative selection of DKO thymocytes is profoundly impaired in a cell-intrinsic manner. Consistent with escape of self-reactive T cells into the periphery, DKO T cells with functional, phenotypic, and transcriptional features of anergy accumulated in chimeric mice. Nevertheless, we observed upregulation of genes encoding inflammatory mediators in anergic DKO T cells, and DKO T cells exhibited enhanced capacity for IL-2 production. These studies reveal cell-intrinsic roles for the NR4A family in both central and peripheral T cell tolerance and demonstrate that each is essential to preserve immune homeostasis.
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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.