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

Nov 11, 2025Arthritis research & therapy

Combined tissue and single-cell gene analysis reveals common and unique immune patterns in Takayasu Arteritis

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

A total of 2,496 (DEGs) were identified in CD4⁺ and CD8⁺ T cells from patients.

CD4⁺ T cells showed enrichment for pathways involved in inflammation, angiogenesis, and platelet activation.
CD8⁺ T cells were primarily associated with cytokine synthesis, particularly related to interleukin-1 signaling.
Both T cell subsets exhibited shared enrichment in pathways related to the complement cascade, focal adhesion, and extracellular matrix organization.
Single-cell analyses indicated significant crosstalk between CD4⁺ and CD8⁺ T cells in the aorta of Takayasu arteritis patients.
EGR1 was consistently up-regulated in both blood and aortic tissue, suggesting a central role in inflammation and a potential therapeutic target.

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BACKGROUND: (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. 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.

Key numbers

851

Number of in from patients.

1,645

Number of in from patients.

EGR1 expression

Number of key genes consistently upregulated in both .

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

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