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Background <p>The airway lesions in COPD are mediated by a variety of inflammatory cells, among which the Th1-dominated delayed-type hypersensitivity response can also cause irreversible damage to normal airways. The immune checkpoint TIGIT and its downstream phosphatase SHIP-1 play a crucial role in coordinating the immune response of CD4 + T cells by regulating the phosphoinositide pathway.</p> Methods <p>This study evaluates the expression patterns of TIGIT/SHIP-1 in CD4 + T cells within the context of smoking-induced COPD and investigates the mechanisms by which TIGIT/SHIP-1 affects CD4 + T cells, also the downstream signaling changes regulating Th1 inflammation. In smoking COPD, we established a research framework encompassing clinical, animal, cellular levels including flow cytometry, immunofluorescence, and chromatin immunoprecipitation.</p> Results <p>We found that CD4 + T cells in smoking COPD exhibit upregulated expression of TIGIT/SHIP-1, and specific knockout of CD4-<i>Tigit</i> and short-term in vivo inhibition of SHIP-1 significantly elevated Th1 levels in emphysematous mice. Through single-cell and bulk-RNA bioinformatics analysis, we identified RelB that regulates COPD-Th1 inflammation by regulates TBX21 in transcriptional level and confirmed its excessive activation in COPD-Th1 inflammation. The PI3K/AKT signaling, acting downstream of TIGIT/SHIP-1, influences the activation of RelB in Th1 cells.</p> Conclusions <p>In smoking-induced COPD, TIGIT/SHIP-1 affects the activation of RelB through the PI3K/AKT pathway, thereby regulating the expression of Th1. It offers insights underlying the immune mechanism of COPD.</p>

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TIGIT/SHIP-1/RelB regulating Th1 inflammation in smoking induced COPD

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月19日

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  • Junyi Ke,
  • Siyu Lei,
  • Zhixiong He,
  • Qinglan Li,
  • Hongchun Huang,
  • Shu Huang,
  • Shiya Lin,
  • Yinying Li,
  • Lixi Lu,
  • Yuanlan Wu,
  • Luxi Lei,
  • Minchao Duan

摘要

Background

The airway lesions in COPD are mediated by a variety of inflammatory cells, among which the Th1-dominated delayed-type hypersensitivity response can also cause irreversible damage to normal airways. The immune checkpoint TIGIT and its downstream phosphatase SHIP-1 play a crucial role in coordinating the immune response of CD4 + T cells by regulating the phosphoinositide pathway.

Methods

This study evaluates the expression patterns of TIGIT/SHIP-1 in CD4 + T cells within the context of smoking-induced COPD and investigates the mechanisms by which TIGIT/SHIP-1 affects CD4 + T cells, also the downstream signaling changes regulating Th1 inflammation. In smoking COPD, we established a research framework encompassing clinical, animal, cellular levels including flow cytometry, immunofluorescence, and chromatin immunoprecipitation.

Results

We found that CD4 + T cells in smoking COPD exhibit upregulated expression of TIGIT/SHIP-1, and specific knockout of CD4-Tigit and short-term in vivo inhibition of SHIP-1 significantly elevated Th1 levels in emphysematous mice. Through single-cell and bulk-RNA bioinformatics analysis, we identified RelB that regulates COPD-Th1 inflammation by regulates TBX21 in transcriptional level and confirmed its excessive activation in COPD-Th1 inflammation. The PI3K/AKT signaling, acting downstream of TIGIT/SHIP-1, influences the activation of RelB in Th1 cells.

Conclusions

In smoking-induced COPD, TIGIT/SHIP-1 affects the activation of RelB through the PI3K/AKT pathway, thereby regulating the expression of Th1. It offers insights underlying the immune mechanism of COPD.