2026-02-19 理化学研究所,徳島大学,東京医科大学
Runxタンパク質のリン酸化による胸腺T細胞の分化運命の制御
<関連情報>
- https://www.riken.jp/press/2026/20260219_2/index.html
- https://www.nature.com/articles/s41590-026-02441-6
Runxタンパク質のリン酸化はヘルパーCD4+ T細胞と細胞傷害性CD8+ T細胞の系統選択を制御する Phosphorylation of Runx protein controls helper CD4+ T cell versus cytotoxic CD8+ T cell lineage choice
Chihiro Ogawa,Kazuki Okuyama,Satoshi Kojo,Kohei Nishino,Hiroaki Machiyama,Aditya K. Padhi,Hirotaka Takahashi,Takashi Ebihara,Mari Tenno,Qin Zhizhen,Sawako Muroi,Kosei Ito,Tatsuya Sawasaki,Kam Y. J. Zhang,Hai-Hui Xue,Tadashi Yokosuka,Hidetaka Kosako & Ichiro Taniuchi
Nature Immunology Published:19 February 2026
DOI:https://doi.org/10.1038/s41590-026-02441-6
Abstract
MHC-I- and MHC-II-selected CD4+CD8+ precursor thymocytes differentiate into cytotoxic CD8+ and helper CD4+ lineage T cells, during which suppression of Cd4 and Thpok genes by Runx-dependent-silencers in those genes is crucial to segregate the two lineages. However, how TCR signals are linked to cytotoxic-lineage-specific Cd4–Thpok silencing remains unclear. Here we show that the terminal Y residue within the evolutionarily conserved C-terminal WRPY motif in Runx1, which is essential for interacting with TLE co-repressor proteins, was phosphorylated more in CD4–CD8+ thymocytes than in CD4+CD8– thymocytes, inducing an interaction with TLE co-repressors for cytotoxic-lineage specific Cd4–Thpok silencing. Non-receptor tyrosine kinases Lck and Zap70 interacted with Runx in the cytoplasm more in MHC-I-signaled CD4–CD8+ thymocytes than in CD4+CD8– thymocytes. Collectively, these findings reveal that differential phosphorylation states at the terminal tyrosine residue in Runx connect MHC restriction with the helper versus cytotoxic T cell lineage choice.
