Splicing factor SF2/ASF rescues IL-2 production in T cells from systemic lupus erythematosus patients by activating IL-2 transcription

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–CD3ζ chain and forced expression of CD3ζ into SLE T cells restores IL-2 production. We recently...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2013-01, Vol.110 (5), p.1845-1850
Hauptverfasser: Moulton, Vaishali R., Grammatikos, Alexandros P., Fitzgerald, Lisa M., Tsokos, George C.
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Sprache:eng
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Zusammenfassung: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–CD3ζ chain and forced expression of CD3ζ 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 CD3ζ 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1214207110