Arginine methylation of FOXP3 is crucial for the suppressive function of regulatory T cells. (February 2019)

• Record Type: Journal Article
• Authors: Kagoya, Yuki; Saijo, Hiroshi; Matsunaga, Yukiko; Guo, Tingxi; Saso, Kayoko; Anczurowski, Mark; Wang, Chung-Hsi; Sugata, Kenji; Murata, Kenji; Butler, Marcus O.; Arrowsmith, Cheryl H.; Hirano, Naoto
• Is Part Of: Journal of autoimmunity. Volume 97(2019)
• Page Start: 10
• Page End: 21
• Publication Date: 2019-02
• Subjects: Regulatory T cells -- FOXP3 -- Posttranslational modification -- Arginine methylation -- PRMT1 -- Graft-versus-host disease; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2018.09.011
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Forkhead box transcription factor 3 (FOXP3) plays a pivotal role in the suppressive function of regulatory T cells. In addition to mRNA levels, FOXP3 activity can also be controlled by posttranslational mechanisms, which have not been studied in a comprehensive manner. Through extensive screening using selective inhibitors, we demonstrate that the inhibition of type I protein arginine methytransferases (PRMTs) attenuates the suppressive functions of regulatory T cells. FOXP3 undergoes methylation on arginine residues at positions 48 and 51 by interacting with protein arginine methyltransferase 1 (PRMT1). The inhibition of arginine methylation confers gene expression profiles representing type I helper T cells to FOXP3 + T cells, which results in attenuated suppressive activity. A methylation-defective mutant of FOXP3 displays less potent activity to suppress xenogeneic graft-versus-host disease in vivo . These results elucidate an important role of arginine methylation to enhance FOXP3 functions and are potentially applicable to modulate regulatory T cell functions. Highlights: Inhibiting arginine methyltransferases attenuates regulatory T cell functions. FOXP3 is arginine-methylated on R48 and 51 by interacting with PRMT1. Arginine methylation in FOXP3 is crucial for its transcriptional activity.