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

Area of Science:

• Immunology
• Genomics
• Vascular Biology

Background:

• Takayasu arteritis (TAK) is a rare, chronic large-vessel vasculitis.
• CD4+ and CD8+ T cells are implicated in TAK pathogenesis, but their specific gene networks are not fully understood.

Purpose of the Study:

• To integrate bulk and single-cell RNA sequencing data to identify mechanistic biomarkers and therapeutic targets for TAK.
• To elucidate the gene expression profiles and intercellular communication networks of T cell subsets in TAK.

Main Methods:

• Bulk RNA sequencing of peripheral CD4+ and CD8+ T cells from TAK patients and healthy controls.
• Single-cell RNA sequencing of aortic tissue from TAK patients and atherosclerotic controls.
• Differential gene expression analysis, functional enrichment, protein-protein interaction network construction, and intercellular communication inference.

Main Results:

• Identified numerous differentially expressed genes (DEGs) in CD4+ and CD8+ T cells, enriched in inflammation, angiogenesis, and cytokine signaling pathways.
• Delineated CD4+-CD8+ T cell crosstalk in TAK aorta and identified heightened protein-homeostasis stress markers.
• Found consistent upregulation of transcriptional regulators EGR1, KLF4, RHOB, and ATF3 in both blood and tissue, with EGR1 playing a central role.

Conclusions:

• Integrated transcriptomics reveals shared and subset-specific T cell signaling in TAK.
• EGR1 is a pivotal molecular switch and a promising therapeutic target for TAK.
• Provides a mechanistic framework for precision immune modulation in large-vessel vasculitis.