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• W1486253993 endingPage "4277" @default.
• W1486253993 startingPage "4268" @default.
• W1486253993 abstract "Abstract Foxp3 plays an essential role in conferring suppressive functionality to CD4+/Foxp3+ regulatory T cells (Tregs). Although studies showed that Foxp3 has to form cooperative complexes with NFAT to bind to target genes, it remains unclear whether NFAT is available in the nucleus of primary Tregs for Foxp3 access. It is generally believed that NFAT in resting cells resides in the cytoplasm, and its nuclear translocation depends on calcineurin (CN) activation. We report that a fraction of NFAT protein constitutively localizes in the nucleus of primary Tregs, where it selectively binds to Foxp3 target genes. Treating Tregs with CN inhibitor does not induce export of NFAT from the nucleus, indicating that its nuclear translocation is independent of CN activity. Consistently, Tregs are resistant to CN inhibitors in the presence of IL-2 and continue to proliferate in response to anti-CD3 stimulation, whereas proliferation of non-Tregs is abrogated by CN inhibitors. In addition, PMA, which activates other transcription factors required for T cell activation but not NFAT, selectively induces Treg proliferation in the absence of ionomycin. TCR interaction with self-MHC class II is not required for PMA-induced Treg proliferation. Tregs expanded by PMA or in the presence of CN inhibitors maintain Treg phenotype and functionality. These findings shed light on Treg biology, paving the way for strategies to selectively activate Tregs." @default.
• W1486253993 created "2016-06-24" @default.
• W1486253993 creator A5031303874 @default.
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• W1486253993 creator A5088523143 @default.
• W1486253993 creator A5090567275 @default.
• W1486253993 creator A5091776399 @default.
• W1486253993 date "2012-05-01" @default.
• W1486253993 modified "2023-09-23" @default.
• W1486253993 title "Constitutive Nuclear Localization of NFAT in Foxp3+ Regulatory T Cells Independent of Calcineurin Activity" @default.
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• W1486253993 doi "https://doi.org/10.4049/jimmunol.1102376" @default.
• W1486253993 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22490438" @default.
• W1486253993 hasPublicationYear "2012" @default.
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