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Induction of PP2A Bβ, a regulator of IL-2 deprivation-induced T-cell apoptosis, is deficient in systemic lupus erythematosus.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 7/26/2011, Vol. 108 Issue 30, p12443-12448, 6p
- Publication Year :
- 2011
-
Abstract
- The activity and substrate specificity of the ubiquitously expressed phosphatase PP2A is determined by the type of regulatory (B) subunit that couples to the catalytic/scaffold core of the enzyme. We determined that the Bβ subunit (PPP2R2B) is expressed in resting T cells, its transcription is down-regulated during T-cell activation, and up-regulated in conditions of low IL-2. Specifically, high levels of PP2A Bβ were produced during IL-2 deprivation-induced apoptosis, whereas Fas ligation had no effect. Forced expression of the Bβ subunit in primary human T cells was sufficient to induce apoptosis, whereas silencing using siRNA protected activated T cells from IL-2 withdrawal-induced cell death. Because T-cell apoptosis is known to be altered in T cells from patients with systemic lupus erythematosus, we analyzed the regulation of PP2A Bβ in this autoimmune disease. We found that levels of PP2A Bβ did not increase upon IL-2 deprivation in 50% of the patients. Remarkably, this defect was accompanied by resistance to apoptosis. Importantly, kinetics of cell death were normal in cells of patients that up-regulated PP2A Bβ in a normal manner. We have identified a unique role for the phosphatase PP2A, particularly the holoenzyme formed by PP2A Bβ. Bβ appears to trigger apoptosis of T cells in the absence of IL-2 and probably contributes to the termination of a no-longer-needed immune response. We propose that defective production of PP2A Bβ upon IL-2 deprivation results in apoptosis resistance and longer survival of autoreactive T cells, in a subset of SLE patients. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 108
- Issue :
- 30
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 63892688
- Full Text :
- https://doi.org/10.1073/pnas.1103915108