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, 2013•National Acad SciencesT 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 …
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