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

VR Moulton, AP Grammatikos… - Proceedings of the …, 2013 - National Acad Sciences
VR Moulton, AP Grammatikos, LM Fitzgerald, GC Tsokos
Proceedings of the National Academy of Sciences, 2013National Acad Sciences
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 …
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.
National Acad Sciences