Serine and arginine rich splicing factor 1 deficiency alters pathways involved in IL-17A expression and is implicated in human psoriasis.

ABSTRACT

Serine and Arginine Rich Splicing Factor 1 (SRSF1) is a splicing factor that binds to exonic enhancers and stimulates splicing and is previously implicated with autoimmunity. Herein, we investigate the role of SRSF1 in regulating innate immune functions that are pertinent in the pathogenesis of auto-inflammatory diseases. Specifically, we show that conditional deletion of SRSF1 in mature lymphocytes resulted in higher expression of il-17a and il-17 f and an expansion of IL17A+ CD8 T cells. Mechanistically, the aberrant expression of IL-17A in SRSF1 cKO mice could not be attributed to alternative splicing of il-17a or il-17 f genes but possibly to defective CD11B+LY6C+ myeloid derived suppressor function in the spleen. Finally, meta-analysis of RNA-Seq collected from psoriasis patients demonstrate a clear correlation between SRSF1 and psoriasis that suggests a putative role of SRSF1 in IL-17A-induced psoriasis.