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

作者：Kang Xu, Taotao Li, Na Gao, Yaxin Zhang, Yi Yang, Honglei Zhao, Longfei Wang, Junming Zhu, Jian Liu, Lili Pan · 发表于：Arthritis Research & Therapy · 年份：2025 · DOI：10.1186/s13075-025-03673-x · 被引用次数：2 · 研究领域：Vasculitis and related conditions、Single-cell and spatial transcriptomics、Atherosclerosis and Cardiovascular Diseases

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 athero...