@article{4febeca0c85f4ceab54bf1f343f6baab,
title = "Arginine methylation of FOXP3 is crucial for the suppressive function of regulatory T cells",
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.",
keywords = "Arginine methylation, FOXP3, Graft-versus-host disease, Posttranslational modification, PRMT1, Regulatory T cells",
author = "Yuki Kagoya and Hiroshi Saijo and Yukiko Matsunaga and Tingxi Guo and Kayoko Saso and Mark Anczurowski and Wang, {Chung Hsi} and Kenji Sugata and Kenji Murata and Butler, {Marcus O.} and Arrowsmith, {Cheryl H.} and Naoto Hirano",
note = "Funding Information: This work was supported by the following grants and fellowships: Japan Society for the Promotion of Science Postdoctoral Fellowship for Overseas Researchers, Japan (YK); Guglietti Fellowship Award, Canada (YK); the Princess Margaret Cancer Foundation, Canada (MOB and NH); Medicine by Design: A Canada First Research Excellence Fund Program at the University of Toronto, Canada (NH); and Ontario Institute for Cancer Research Clinical Investigator Award, Canada, IA-039 (NH). The Structural Genomics Consortium (SGC) is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada through Ontario Genomics Institute, Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766], Janssen, Merck & Co., Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, S{\~a}o Paulo Research Foundation-FAPESP, Takeda, and the Wellcome Trust. Funding Information: This work was supported by the following grants and fellowships: Japan Society for the Promotion of Science Postdoctoral Fellowship for Overseas Researchers, Japan (YK); Guglietti Fellowship Award, Canada (YK); the Princess Margaret Cancer Foundation, Canada (MOB and NH); Medicine by Design: A Canada First Research Excellence Fund Program at the University of Toronto, Canada (NH); and Ontario Institute for Cancer Research Clinical Investigator Award, Canada, IA-039 (NH). The Structural Genomics Consortium (SGC) is a registered charity (number 1097737 ) that receives funds from AbbVie , Bayer Pharma AG , Boehringer Ingelheim , Canada Foundation for Innovation , Eshelman Institute for Innovation , Genome Canada through Ontario Genomics Institute , Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766 ], Janssen, Merck & Co., Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, S{\~a}o Paulo Research Foundation-FAPESP, Takeda, and the Wellcome Trust. Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",
year = "2019",
month = feb,
doi = "10.1016/j.jaut.2018.09.011",
language = "English",
volume = "97",
pages = "10--21",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",
}