Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 115, Issue 11, Pages 3193-3204Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI24895
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Funding
- NIAID NIH HHS [R01 AI49954, R01 AI42269, R01 AI042269, R01 AI049954] Funding Source: Medline
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Decreased IL-2 production in systemic lupus erythematosus (SLE) represents a central component of the disease immunopathology. We report that the message, protein, and enzymatic activity of the catalytic subunit of protein phosphatase 2A (PP2Ac), but not PP1, are increased in patients with SLE regardless of disease activity and treatment and in a disease-specific manner. Treatment of SLE T cells with PP2Ac-siRNA decreased the protein levels and activity of PP2Ac in a specific manner and increased the levels of phosphorylated cAMP response element-binding protein and its binding to the IL2 and c-fos promoters, as well as increased activator protein I activity, causing normalization of IL-2 production. Our data document increased activity of PP2A as a novel SLE disease-specific abnormality and define a distinct mechanism whereby it represses IL-2 production. We propose the use of PP2Ac-siRNA as a novel tool to correct T cell IL-2 production in SLE patients.
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