Scholarlink

Background <p>Takayasu arteritis (TAK) is a rare, chronic large-vessel vasculitis. Although CD4⁺ and CD8⁺ T cells are acknowledged drivers of vascular injury in TAK, the gene networks that confer their pathogenicity remain incompletely mapped.</p> Objectives <p>This study aimed to integrate bulk RNA-sequencing of peripheral-blood T-cell subsets with single-cell RNA-sequencing of aortic tissue to find mechanistic biomarkers and therapeutic targets for TAK.</p> Methods <p>We performed bulk RNA-sequencing on peripheral-blood CD4⁺ and CD8⁺ T cells from eight treatment-naïve TAK patients and three age matched healthy controls. In parallel, single-cell RNA-sequencing was applied to aortic tissue from three additional TAK patients and three atherosclerotic controls. DEGs were defined at false-discovery rate &lt; 0.05. Functional enrichment used Gene Ontology, KEGG and Reactome. STRING constructed protein–protein interaction networks, and Cell Chat inferred intercellular ligand–receptor communication.</p> Results <p>Bulk profiling identified 851 DEGs in CD4⁺ and 1 645 DEGs in CD8⁺ T cells. CD4⁺ DEGs were enriched for inflammation, angiogenesis and platelet-activation pathways; CD8⁺ DEGs concentrated on cytokine synthesis, notably interleukin-1 signaling. Both subsets shared enrichment in complement cascade, focal adhesion and extracellular-matrix organization, indicating convergent pro-inflammatory programs. Single-cell analyses delineated dense CD4⁺– CD8⁺ crosstalk within TAK aorta and, relative to atherosclerotic controls, heat-shock protein binding and ubiquitin-ligase activity—hallmarks of heightened protein-homeostasis stress. Four transcriptional regulators—EGR1, KLF4, RHOB and ATF3—were consistently up-regulated in both blood and tissue; EGR1 showed the strongest fold-change and occupied a central hub in protein-interaction and ligand–receptor networks. In peripheral cells EGR1 co-clustered with cytokine-biosynthetic modules, while in tissue its profile mirrored the composite CD4⁺ and CD8⁺ signature, underscoring a unifying role in systemic and local inflammation.</p> Conclusions <p>Integrated bulk and single-cell transcriptomics reveal both shared and subset-specific signaling landscapes for CD4⁺ and CD8⁺ T cells in TAK. The consistent prominence of EGR1 across compartments nominates this factor as a pivotal molecular switch and attractive therapeutic target. These data furnish a mechanistic framework for precision immune modulation in large-vessel vasculitis.</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

Integrated bulk and single-cell transcriptomics identifies shared and specific immune signatures in Takayasu Arteritis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月11日

查看全文
  • Kexin Xu,
  • Taotao Li,
  • Na Gao,
  • Yaxin Zhang,
  • Yi Yang,
  • Honglei Zhao,
  • Longfei Wang,
  • Junming Zhu,
  • Jian Liu,
  • Lili Pan

摘要

Background

Takayasu arteritis (TAK) is a rare, chronic large-vessel vasculitis. Although CD4⁺ and CD8⁺ T cells are acknowledged drivers of vascular injury in TAK, the gene networks that confer their pathogenicity remain incompletely mapped.

Objectives

This study aimed to integrate bulk RNA-sequencing of peripheral-blood T-cell subsets with single-cell RNA-sequencing of aortic tissue to find mechanistic biomarkers and therapeutic targets for TAK.

Methods

We performed bulk RNA-sequencing on peripheral-blood CD4⁺ and CD8⁺ T cells from eight treatment-naïve TAK patients and three age matched healthy controls. In parallel, single-cell RNA-sequencing was applied to aortic tissue from three additional TAK patients and three atherosclerotic controls. DEGs were defined at false-discovery rate < 0.05. Functional enrichment used Gene Ontology, KEGG and Reactome. STRING constructed protein–protein interaction networks, and Cell Chat inferred intercellular ligand–receptor communication.

Results

Bulk profiling identified 851 DEGs in CD4⁺ and 1 645 DEGs in CD8⁺ T cells. CD4⁺ DEGs were enriched for inflammation, angiogenesis and platelet-activation pathways; CD8⁺ DEGs concentrated on cytokine synthesis, notably interleukin-1 signaling. Both subsets shared enrichment in complement cascade, focal adhesion and extracellular-matrix organization, indicating convergent pro-inflammatory programs. Single-cell analyses delineated dense CD4⁺– CD8⁺ crosstalk within TAK aorta and, relative to atherosclerotic controls, heat-shock protein binding and ubiquitin-ligase activity—hallmarks of heightened protein-homeostasis stress. Four transcriptional regulators—EGR1, KLF4, RHOB and ATF3—were consistently up-regulated in both blood and tissue; EGR1 showed the strongest fold-change and occupied a central hub in protein-interaction and ligand–receptor networks. In peripheral cells EGR1 co-clustered with cytokine-biosynthetic modules, while in tissue its profile mirrored the composite CD4⁺ and CD8⁺ signature, underscoring a unifying role in systemic and local inflammation.

Conclusions

Integrated bulk and single-cell transcriptomics reveal both shared and subset-specific signaling landscapes for CD4⁺ and CD8⁺ T cells in TAK. The consistent prominence of EGR1 across compartments nominates this factor as a pivotal molecular switch and attractive therapeutic target. These data furnish a mechanistic framework for precision immune modulation in large-vessel vasculitis.