title: Splicing factor SF2/ASF rescues IL-2 production in T cells from systemic lupus erythematosus patients by activating IL-2 transcription.
abstract: 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.
authors: Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA. vmoulton@bidmc.harvard.edu
authors: Vaishali R
authors: VR
authors: Moulton
authors: Alexandros P
authors: AP
authors: Grammatikos
authors: Lisa M
authors: LM
authors: Fitzgerald
authors: George C
authors: GC
authors: Tsokos
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D015533:Transcriptional Activation; D055815:Young Adult
chemical_list: D007376:Interleukin-2; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D000068103:Serine-Arginine Splicing Factors