Journal article
Constitutive Nuclear Localization of NFAT in Foxp3(+) Regulatory T Cells Independent of Calcineurin Activity
The Journal of immunology (1950), Vol.188(9), pp.4268-4277
05/01/2012
DOI: 10.4049/jimmunol.1102376
PMID: 22490438
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. The Journal of Immunology, 2012, 188: 4268-4277.
Details
- Title: Subtitle
- Constitutive Nuclear Localization of NFAT in Foxp3(+) Regulatory T Cells Independent of Calcineurin Activity
- Creators
- Qiuxia Li - University of UtahArvind Shakya - University of UtahXiaohua Guo - University of UtahHongbo Zhang - Xi'an Jiaotong UniversityDean Tantin - University of UtahPeter E. Jensen - University of UtahXinjian Chen - University of Utah
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.188(9), pp.4268-4277
- DOI
- 10.4049/jimmunol.1102376
- PMID
- 22490438
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- Amer Assoc Immunologists
- Number of pages
- 10
- Language
- English
- Date published
- 05/01/2012
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359679502771
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