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Nat Immunol. 2018 Nov;19(11):1265-1276. doi: 10.1038/s41590-018-0222-z. Epub 2018 Oct 15.

Arginine methylation controls the strength of γc-family cytokine signaling in T cell maintenance.

Author information

1
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
2
Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
3
Department of Pharmacology, Showa University School of Dentistry, Shinagawa-ku, Tokyo, Japan.
4
Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
5
Division of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
6
Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
7
JST, Precursory Research for Embryonic Science and Technology (PRESTO), Bunkyo-ku, Tokyo, Japan.
8
Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Bunkyo-ku, Tokyo, Japan.
9
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. takayana@m.u-tokyo.ac.jp.

Abstract

The methylation of arginine residues in proteins is a post-translational modification that contributes to a wide range of biological processes. Many cytokines involved in T cell development and activation utilize the common cytokine receptor γ-chain (γc) and the kinase JAK3 for signal transduction, but the regulatory mechanism that underlies the expression of these factors remains unclear. Here we found that the arginine methyltransferase PRMT5 was essential for the maintenance of invariant natural killer T cells (iNKT cells), CD4+ T cells and CD8+ T cells. T cell-specific deletion of Prmt5 led to a marked reduction in signaling via γc-family cytokines and a substantial loss of thymic iNKT cells, as well as a decreased number of peripheral CD4+ T cells and CD8+ T cells. PRMT5 induced the symmetric dimethylation of Sm proteins that promoted the splicing of pre-mRNA encoding γc and JAK3, and this critically contributed to the expression of γc and JAK3. Thus, arginine methylation regulates strength of signaling via γc-family cytokines by facilitating the expression of signal-transducing components.

PMID:
30323341
DOI:
10.1038/s41590-018-0222-z

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