2026年新着論文 10　細胞情報学分野から論文が発表されました

Phosphorylation of Runx protein controls helper CD4⁺ T cell versus cytotoxic CD8⁺ T cell lineage choice

Nat Immunol. 2026 Feb 19. doi: 10.1038/s41590-026-02441-6. Online ahead of print.

Authors

Chihiro Ogawa^#¹, Kazuki Okuyama^#¹, Satoshi Kojo^#^1 2, Kohei Nishino³, Hiroaki Machiyama⁴, Aditya K Padhi^5 6, Hirotaka Takahashi⁷, Takashi Ebihara^1 8, Mari Tenno^1 9, Qin Zhizhen¹, Sawako Muroi¹, Kosei Ito¹⁰, Tatsuya Sawasaki⁷, Kam Y J Zhang^5 11, Hai-Hui Xue¹², Tadashi Yokosuka⁴, Hidetaka Kosako³, Ichiro Taniuchi¹³

Affiliations

¹ Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan.
² Department of Immunology and Stem Cell Biology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
³ Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
⁴ Department of Immunology, Tokyo Medical University, Tokyo, Japan.
⁵ Laboratory for Structural Bioinformatics, RIKEN Center for Biosystems Dynamics Research, Yokohama, Kanagawa, Japan.
⁶ Laboratory for Computational Biology and Biomolecular Design, School of Biochemical Engineering, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh, India.
⁷ Division of Cell-Free Science, Proteo-Science Center, Ehime University, Matsuyama, Ehime, Japan.
⁸ Department of Medical Biology, Akita University Graduate School of Medicine, Akita, Japan.
⁹ Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
¹⁰ Department of Molecular Tumor Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
¹¹ Laboratory for Computational Molecular Design, Center for Biosystems Dynamics Research, RIKEN, Yokohama, Kanagawa, Japan.
¹² Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, NJ, USA.
¹³ Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan. ichiro.taniuchi@riken.jp.

^# Contributed equally.

PMID: 41714737
DOI: 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.

Conflict of interest statement

Competing interests: Authors declare no competing interests.

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