Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 5, Pages 1845-1850Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1214207110
Keywords
autoimmunity; SFRS1; T lymphocyte; interleukin-2
Categories
Funding
- National Institutes of Health [R01 AI42269, K01 AR060781]
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T cells from patients with systemic lupus erythematosus (SLE) produce insufficient amounts of the vital cytokine IL-2. We previously showed that SLE T cells express decreased levels of the T-cell receptor-CD3 zeta chain and forced expression of CD3 zeta into SLE T cells restores IL-2 production. We recently showed that the serine arginine protein splicing factor 2/alternative splicing factor (SF2/ASF) enhances the expression of CD3 zeta chain by limiting the production of an unstable splice variant. Here we demonstrate that SF2/ASF levels are decreased in patients with SLE and more so in those with active disease. More importantly, we reveal a function of SF2/ASF, independent of T-cell receptor/CD3 signaling, whereby it is recruited to the IL-2 promoter, increases transcriptional activity, and enhances IL-2 production in SLE T cells. Our results demonstrate that SF2/ASF regulates IL-2 production and that decreased SF2/ASF expression in SLE T cells contributes to deficient IL-2 production.
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