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

Shi Su; Xanthi-Lida Katopodi; Yered H Pita-Juarez; Emanual Maverakis; Ioannis S Vlachos; Iannis E Adamopoulos

doi:10.1016/j.clim.2022.109041

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

Clin Immunol. 2022 Jul:240:109041. doi: 10.1016/j.clim.2022.109041. Epub 2022 May 22.

Authors

Shi Su¹, Xanthi-Lida Katopodi², Yered H Pita-Juarez², Emanual Maverakis³, Ioannis S Vlachos⁴, Iannis E Adamopoulos⁵

Affiliations

¹ Department of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
² Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
³ Department of Dermatology, University of California, Davis, Sacramento, CA, USA.
⁴ Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Harvard Medical School Initiative for RNA Medicine, Boston, MA, USA; Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Department of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: Iadamopo@bidmc.harvard.edu.

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.

Keywords: Alternative splicing; Autoimmunity; Il-17; Psoriasis; SRSF1.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Alternative Splicing
Animals
Arginine / genetics
Arginine / metabolism
Humans
Interleukin-17* / metabolism
Mice
Psoriasis* / genetics
RNA Splicing Factors / genetics
RNA Splicing Factors / metabolism
Serine / genetics
Serine / metabolism
Serine-Arginine Splicing Factors / genetics
Serine-Arginine Splicing Factors / metabolism

Substances

Interleukin-17
RNA Splicing Factors
SRSF1 protein, human
Serine-Arginine Splicing Factors
Serine
Arginine

Abstract

Publication types

MeSH terms

Substances

Grants and funding