Scholarlink

<p>The role of CD8<sup>+</sup> tissue-resident memory T (CD8<sup>+</sup> T<sub>RM</sub>) in inflammation is well established. However, the mechanisms by which CD8<sup>+</sup> T<sub>RM</sub> cells are activated in tissues have remained elusive. Here, we show that Leucine zipper-like transcription regulator 1 (LZTR1), a substrate adaptor for cullin3 (CUL3) ubiquitin ligase complex, regulates CD8<sup>+</sup> T<sub>RM</sub> activation and proliferation in cutaneous and colonic epithelia through modulation of major histocompatibility complex class I (MHC-I) expression in an NF-κB1-dependent manner. Mechanistically, LZTR1 modulates MHC-I transcription by regulating co-translational biogenesis of NF-κB1 (p50) in a ubiquitination-independent but proteasome-dependent manner through direct binding with ribosome and proteasome. Loss of LZTR1 leads to suppression of CD8<sup>+</sup> T<sub>RM</sub> activation and proliferation and decreased production of IL-17A with blunting of inflammatory responses in both cutaneous and gut epithelia in vivo. In summary, these data identify LZTR1 as a novel regulator of CD8<sup>+</sup> T<sub>RM</sub> function and provide insights into the mechanisms that drive and maintain CD8<sup>+</sup> T-cell responses in epithelial-associated autoimmune diseases.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

LZTR1 regulates epithelial MHC-I expression via NF-κB1 to modulate CD8+ T cells activation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月29日

查看全文
  • Rundong Jiang,
  • Zhiqin Fang,
  • Yutong Wang,
  • Bo Huang,
  • Junkun Liu,
  • Lam C. Tsoi,
  • Rachael Bogle,
  • Zongbo Zhang,
  • Yehong Kuang,
  • Xin Li,
  • Liang Dong,
  • Liping Jin,
  • Johann E. Gudjonsson,
  • Mingzhu Yin,
  • Xiang Chen

摘要

The role of CD8+ tissue-resident memory T (CD8+ TRM) in inflammation is well established. However, the mechanisms by which CD8+ TRM cells are activated in tissues have remained elusive. Here, we show that Leucine zipper-like transcription regulator 1 (LZTR1), a substrate adaptor for cullin3 (CUL3) ubiquitin ligase complex, regulates CD8+ TRM activation and proliferation in cutaneous and colonic epithelia through modulation of major histocompatibility complex class I (MHC-I) expression in an NF-κB1-dependent manner. Mechanistically, LZTR1 modulates MHC-I transcription by regulating co-translational biogenesis of NF-κB1 (p50) in a ubiquitination-independent but proteasome-dependent manner through direct binding with ribosome and proteasome. Loss of LZTR1 leads to suppression of CD8+ TRM activation and proliferation and decreased production of IL-17A with blunting of inflammatory responses in both cutaneous and gut epithelia in vivo. In summary, these data identify LZTR1 as a novel regulator of CD8+ TRM function and provide insights into the mechanisms that drive and maintain CD8+ T-cell responses in epithelial-associated autoimmune diseases.