Artikel ; Online: Divergent effects of calcineurin Aβ on regulatory and conventional T-cell homeostasis.
Clinical immunology (Orlando, Fla.)
2011 Band 138, Heft 3, Seite(n) 321–330
Abstract: 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 ... ...
Abstract | 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. |
---|---|
Mesh-Begriff(e) | Animals ; Calcineurin/genetics ; Calcineurin/immunology ; Cytokines/biosynthesis ; Cytokines/immunology ; Forkhead Transcription Factors/immunology ; Hepatomegaly/immunology ; Hepatomegaly/metabolism ; Homeostasis/immunology ; Lymphocyte Activation/immunology ; Mice ; Mice, Mutant Strains ; Proto-Oncogene Proteins c-bcl-2/biosynthesis ; Proto-Oncogene Proteins c-bcl-2/immunology ; Signal Transduction/immunology ; Splenomegaly/immunology ; Splenomegaly/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Transforming Growth Factor beta/immunology |
Chemische Substanzen | Cytokines ; Forkhead Transcription Factors ; Foxp3 protein, mouse ; Proto-Oncogene Proteins c-bcl-2 ; Transforming Growth Factor beta ; Calcineurin (EC 3.1.3.16) ; protein phosphatase 3, catalytic subunit, beta isoform, mouse (EC 3.1.3.16) |
Sprache | Englisch |
Erscheinungsdatum | 2011-01-20 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
ZDB-ID | 1459903-x |
ISSN | 1521-7035 ; 1521-6616 |
ISSN (online) | 1521-7035 |
ISSN | 1521-6616 |
DOI | 10.1016/j.clim.2010.12.020 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Volltext online
Zusatzmaterialien
Kategorien
Verfügbar in ZB MED Köln/Königswinter
Zs.A 880: Hefte anzeigen | Standort: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.