| First Author | Doetschman T | Year | 2011 |
| Journal | Clin Immunol | Volume | 138 |
| Issue | 3 | Pages | 321-30 |
| PubMed ID | 21256088 | Mgi Jnum | J:169414 |
| Mgi Id | MGI:4940946 | Doi | 10.1016/j.clim.2010.12.020 |
| Citation | Doetschman T, et al. (2011) Divergent effects of calcineurin Abeta on regulatory and conventional T-cell homeostasis. Clin Immunol 138(3):321-30 |
| abstractText | 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 Abeta (CNAbeta). 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 IFNgamma). FOXP3(+) T(reg) cells were significantly decreased in Cnab(-/-) mice likely contributing to increased T-cell activation. Interestingly, we found that CNAbeta is critical for promotion of BCL-2 expression in FOXP3(+) T(reg) and for permitting TGFbeta signaling, as TGFbeta induces FOXP3 in control but not in Cnab(-/-) T-cells. Together, these data suggest that CNAbeta is important for the production and maintenance of T(reg) cells and to ensure mature T-cell quiescence. |
