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<p>MHC-I- and MHC-II-selected CD4<sup>+</sup>CD8<sup>+</sup> precursor thymocytes differentiate into cytotoxic CD8<sup>+</sup> and helper CD4<sup>+</sup> lineage T cells, during which suppression of <i>Cd4</i> and <i>Thpok</i> 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 <i>Cd4</i>-<i>Thpok</i> 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<sup>−</sup>CD8<sup>+</sup> thymocytes than in CD4<sup>+</sup>CD8<sup>−</sup> thymocytes, inducing an interaction with TLE co-repressors for cytotoxic-lineage specific <i>Cd4</i>-<i>Thpok</i> silencing. Non-receptor tyrosine kinases Lck and Zap70 interacted with Runx in the cytoplasm more in MHC-I-signaled CD4<sup>−</sup>CD8<sup>+</sup> thymocytes than in CD4<sup>+</sup>CD8<sup>−</sup> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月19日

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  • 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

摘要

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.