Divergent effects of calcineurin Aβ on regulatory and conventional T-cell homeostasis
Copyright © 2010 Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 138(2011), 3 vom: 28. März, Seite 321-30 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2011
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Cytokines Forkhead Transcription Factors Foxp3 protein, mouse Proto-Oncogene Proteins c-bcl-2 Transforming Growth Factor beta Calcineurin EC 3.1.3.16 |
| Zusammenfassung: | Copyright © 2010 Elsevier Inc. All rights reserved. Calcineurin (CN) is a phosphatase that activates nuclear factor of activated T cells (NFAT). While the CN inhibitors cyclosporine A (CsA) and tacrolimus (FK506) can prevent graft rejection, they also cause inflammatory diseases. We investigated the role of calcineurin using mice deficient in the CN catalytic subunit Aβ (CNAβ). Cnab(-/-) mice exhibit defective thymocyte maturation, splenomegaly and hepatomegaly. Further, as Cnab(-/-) mice age, they exhibit spontaneous T-cell activation and enhanced production of proinflammatory cytokines (IL-4, IL-6, and IFNγ). FOXP3(+) T(reg) cells were significantly decreased in Cnab(-/-) mice likely contributing to increased T-cell activation. Interestingly, we found that CNAβ is critical for promotion of BCL-2 expression in FOXP3(+) T(reg) and for permitting TGFβ signaling, as TGFβ induces FOXP3 in control but not in Cnab(-/-) T-cells. Together, these data suggest that CNAβ is important for the production and maintenance of T(reg) cells and to ensure mature T-cell quiescence |
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| Beschreibung: | Date Completed 14.04.2011 Date Revised 20.10.2021 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2010.12.020 |