ArticlePloS one2014
Nfatc2 and Tob1 have non-overlapping function in T cell negative regulation and tumorigenesis.
Article in PloS one, 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, 14 citations in OpenAlex.
- Small-molecule NFAT signaling inhibitor with dual NFATc1/NFATc2 activity and limited calcineurin catalytic inhibition.Archives of pharmacal research · 2026Article
- Association among Noncoding-RNAs, APRO Family Proteins, and Gut Microbiota in the Development of Breast Cancer.Oncology research · 2025Review
- A Novel Homozygous Six Base Pair Deletion Found in the NFATC2 Gene in a Patient with EBV-Associated Lymphoproliferation.Journal of clinical immunology · 2024Article
- Rare diseases of epigenetic origin: Challenges and opportunities.Frontiers in genetics · 2023Review
- Transgenic expression of a T cell epitope in Strongyloides ratti reveals that helminth-specific CD4+ T cells constitute both Th2 and Treg populations.PLoS pathogens · 2021Article
- Isoform-Selective NFAT Inhibitor: Potential Usefulness and Development.International journal of molecular sciences · 2021Review
- Transcriptomic Analysis Exploring the Molecular Mechanisms of Hanchuan Zupa Granules in Alleviating Asthma in Rat.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- NFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.PloS one · 2021Article
- Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function.The Journal of clinical investigation · 2020Article
- Differential genetic and functional background in inflammatory bowel disease phenotypes of a Greek population: a systems bioinformatics approach.Gut pathogens · 2019Article
- NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes.Cell cycle (Georgetown, Tex.) · 2016Article
- Cell cycle and apoptosis regulation by NFAT transcription factors: new roles for an old player.Cell death & disease · 2016Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Nfatc2 and Tob1 are intrinsic negative regulators of T cell activation. Nfatc2-deficient and Tob1-deficient T cells show reduced thresholds of activation; however, whether these factors have independent or overlapping roles in negative regulation of T cell responses has not been previously examined. Here, we show that Nfatc2 knockout (KO) but not Tob1 KO mice have age-associated accumulation of persistently activated T cells in vivo and expansion of the CD44+ memory cell compartment and age-associated lymphocytic infiltrates in visceral organs, without significant changes in numbers of CD4+CD25+Foxp3+ regulatory T cells (Treg). In vitro, CD4+CD25- "conventional" T cells (Tconvs) from both KO strains showed greater proliferation than wild type (WT) Tconvs. However, while Tregs from Nfatc2 KO mice retained normal suppressive function, Tregs from Tob1 KOs had enhanced suppressive activity. Nfatc2 KO Tconvs expanded somewhat more rapidly than WT Tconvs under conditions of homeostatic proliferation, but their accelerated growth capacity was negated, at least acutely, in a lymphoreplete environment. Finally, Nfatc2 KO mice developed a previously uncharacterized increase in B-cell malignancies, which was not accelerated by the absence of Tob1. The data thus support the prevailing hypothesis that Nfatc2 and Tob1 are non-redundant regulators of lymphocyte 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.