HuR Ablation Destabilizes Foxp3 mRNA and Impairs Regulatory T Cell Function, Contributing to an Autoimmune Phenotype

The study investigates the role of the RNA-binding protein HuR in regulatory T cell (Treg) function using a Foxp3YFP/Cre HuRfl/fl mouse model. It demonstrates that HuR directly binds and stabilizes Foxp3 mRNA, which is crucial for Treg function and immune regulation. In HuR-deficient mice, Foxp3 mRNA stability and expression were significantly reduced, leading to impaired Treg function and an autoimmune phenotype characterized by symptoms such as hair loss and multi-organ immune cell infiltration. The study highlights the disruption of T cell differentiation pathways, particularly involving RORγt, and suggests that HuR-mediated regulation is essential for maintaining Foxp3 expression and immune homeostasis.