biostudies-literatureKatsuyama TNIAID NIH HHSNIAMS NIH HHSNIHSICPA5411-5423https://www.ebi.ac.uk/biostudies/studies/S-EPMC6877308biostudies-literatureUnknown129(12)Systemic lupus erythematosus (SLE) is a devastating autoimmune disease in which hyperactive T cells play a critical role. Understanding molecular mechanisms underlying the T cell hyperactivity will lead to identification of specific therapeutic targets. Serine/arginine-rich splicing factor 1 (SRSF1) is an essential RNA-binding protein that controls posttranscriptional gene expression. We have demonstrated that SRSF1 levels are aberrantly decreased in T cells from patients with SLE and that they correlate with severe disease, yet the role of SRSF1 in T cell physiology and autoimmune disease is largely unknown. Here we show that T cell-restricted Srsf1-deficient mice develop systemic autoimmunity and lupus-nephritis. Mice exhibit increased frequencies of activated/effector T cells producing The Journal of clinical investigationSplicing factor SRSF1 controls T cell hyperactivity and systemic autoimmunity.PMC6877308R01AI42269K01 AR060781xxxxR01 AI042269R01 AR068974Li HComte DKatsuyama TTsokos GCMoulton VRfalseSplicing factor SRSF1 controls T cell hyperactivity and systemic autoimmunity.Systemic lupus erythematosus (SLE) is a devastating autoimmune disease in which hyperactive T cells play a critical role. Understanding molecular mechanisms underlying the T cell hyperactivity will lead to identification of specific therapeutic targets. Serine/arginine-rich splicing factor 1 (SRSF1) is an essential RNA-binding protein that controls posttranscriptional gene expression. We have demonstrated that SRSF1 levels are aberrantly decreased in T cells from patients with SLE and that they correlate with severe disease, yet the role of SRSF1 in T cell physiology and autoimmune disease is largely unknown. Here we show that T cell-restricted Srsf1-deficient mice develop systemic autoimmunity and lupus-nephritis. Mice exhibit increased frequencies of activated/effector T cells producing 2019-01-01T00:00:00Z2019 Dec2025-04-26T01:28:29.461Z2025-04-06T10:02:59.494ZS-EPMC68773083148726810.1172/jci12794910.1172/JCI127949