The effect of inhibition of arginine methylation in human FOXP3-transduced T cells

The forkhead box transcription factor 3 (FOXP3) plays a pivotal role in the suppressive function of regulatory T cells. Protein function is diversely controlled by posttranslational mechanisms as well as mRNA expression levels. In this study, we demonstrate that FOXP3 undergoes arginine methylation by interacting with the protein arginine methyltransferase 1 (PRMT1). The inhibition of arginine methylation conferred gene expression profiles representing type I helper T cells to FOXP3+ T cells, which resulted in attenuated suppressive activity. A methylation-defective mutant of FOXP3 displayed less potent activity to suppress xenogeneic graft-versus-host disease in vivo. Human CD4+ T cells derived from three different donors were transduced with control DNGFR or FOXP3-DNGFR and cultured in the presence of DMSO or MS023 (type I PRMT inhibitor). The DNGFR+ cells were isolated on day 7, and the gene expression profiles were analyzed using the Affymetrix PrimeView™ Human Gene Expression Array.