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

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• Regulatory T (Treg) cells are vital for immune homeostasis and preventing autoimmune diseases.
• The molecular mechanisms governing Treg cell function and plasticity are not fully elucidated.
• Reduced serine/arginine-rich splicing factor 1 (SRSF1) levels are observed in T cells from systemic lupus erythematosus patients.

Purpose of the Study:

• To investigate the role of SRSF1 in Treg cell homeostasis and function.
• To understand the molecular pathways linking SRSF1 to Treg cell-mediated immune control.
• To explore the implications of SRSF1 deficiency in Treg cells for autoimmune pathogenesis.

Main Methods:

• Conditional gene deletion of SRSF1 in Treg cells.
• Analysis of Treg cell metabolism, including glycolytic activity.
• Assessment of mTORC1 signaling pathway activation.
• Measurement of pro-inflammatory cytokine production.
• Evaluation of autoimmune development and organ inflammation in vivo.

Main Results:

• Conditional absence of SRSF1 in Treg cells leads to profound autoimmunity and organ inflammation.
• SRSF1 deficiency elevates glycolytic metabolism and mTORC1 activity in Treg cells.
• Loss of SRSF1 promotes the production of pro-inflammatory cytokines by Treg cells.
• SRSF1 is essential for maintaining Treg cell homeostasis and proper immune regulation.

Conclusions:

• SRSF1 is a critical molecular regulator of Treg cell function and plasticity.
• Altered Treg cell metabolism and function due to SRSF1 deficiency contribute to autoimmune disease pathogenesis.
• These findings provide novel insights into the molecular mechanisms underlying autoimmune diseases like systemic lupus erythematosus.