Arginine methylation of FOXP3 is crucial for the suppressive function of regulatory T cells

Yuki Kagoya, Hiroshi Saijo, Yukiko Matsunaga, Tingxi Guo, Kayoko Saso, Mark Anczurowski, Chung Hsi Wang, Kenji Sugata, Kenji Murata, Marcus O. Butler, Cheryl H. Arrowsmith, Naoto Hirano

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10-21
Number of pages12
JournalJournal of Autoimmunity
Volume97
DOIs
Publication statusPublished - 2019 Feb
Externally publishedYes

Keywords

  • Arginine methylation
  • FOXP3
  • Graft-versus-host disease
  • PRMT1
  • Posttranslational modification
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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