Splicing factor SRSF1 is indispensable for regulatory T cell homeostasis and function

Cell Rep. 2021 Jul 6;36(1):109339. doi: 10.1016/j.celrep.2021.109339.

Abstract

The ability of regulatory T (Treg) cells to control the immune response and limit the development of autoimmune diseases is determined by distinct molecular processes, which are not fully understood. We show here that serine/arginine-rich splicing factor 1 (SRSF1), which is decreased in T cells from patients with systemic lupus erythematosus, is necessary for the homeostasis and proper function of Treg cells, because its conditional absence in these cells leads to profound autoimmunity and organ inflammation by elevating the glycolytic metabolism and mTORC1 activity and the production of proinflammatory cytokines. Our data reveal a molecular mechanism that controls Treg cell plasticity and offer insights into the pathogenesis of autoimmune disease.

Keywords: SRSF1; T cells; Treg; autoimmunity; cytokines; immune homeostasis; immune regulation; inflammation; mTOR pathway; splicing factor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Plasticity
  • Cell Survival
  • Gene Deletion
  • Glycolysis
  • Heterozygote
  • Homeostasis*
  • Inflammation / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Serine-Arginine Splicing Factors / deficiency
  • Serine-Arginine Splicing Factors / metabolism*
  • Sirolimus / pharmacology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes, Regulatory / immunology
  • Transcriptome / genetics

Substances

  • Srsf1 protein, mouse
  • Serine-Arginine Splicing Factors
  • Sirolimus