Single cell transcriptomics reveals recent CD8T cell receptor signaling in patients with coronary artery disease

Shahad Iqneibi; Ryosuke Saigusa; Amir Khan; Mohammad Oliaeimotlagh; Sujit Silas Armstrong Suthahar; Sunil Kumar; Ahmad Alimadadi; Christopher P. Durant; Yanal Ghosheh; Coleen A. McNamara; Catherine C. Hedrick; Klaus Ley

doi:10.3389/fimmu.2023.1239148

Single cell transcriptomics reveals recent CD8T cell receptor signaling in patients with coronary artery disease

Shahad Iqneibi, Ryosuke Saigusa, Amir Khan, Mohammad Oliaeimotlagh, Sujit Silas Armstrong Suthahar, Sunil Kumar, Ahmad Alimadadi, Christopher P. Durant, Yanal Ghosheh, Coleen A. McNamara, Catherine C. Hedrick, Klaus Ley

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Coronary artery disease (CAD) is a major cause of death worldwide. The role of CD8+ T cells in CAD is unknown. Recent studies suggest a breakdown of tolerance in atherosclerosis, resulting in active T cell receptor (TCR) engagement with self-antigens. We hypothesized that TCR engagement would leave characteristic gene expression signatures. In a single cell RNA-sequencing analysis of CD8+ T cells from 30 patients with CAD and 30 controls we found significant enrichment of TCR signaling pathways in CAD+ subjects, suggesting recent TCR engagement. We also found significant enrichment of cytotoxic and exhaustion pathways in CAD cases compared to controls. Highly significant upregulation of TCR signaling in CAD indicates that CD8 T cells reactive to atherosclerosis antigens are prominent in the blood of CAD cases compared to controls.

Original language	English (US)
Article number	1239148
Journal	Frontiers in immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1239148
State	Published - 2023
Externally published	Yes

Keywords

CAD
CD8 T cells
CITE-Seq
atherosclerosis
scRNA-seq
tolerance

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.3389/fimmu.2023.1239148

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Iqneibi, S., Saigusa, R., Khan, A., Oliaeimotlagh, M., Armstrong Suthahar, S. S., Kumar, S., Alimadadi, A., Durant, C. P., Ghosheh, Y., McNamara, C. A., Hedrick, C. C., & Ley, K. (2023). Single cell transcriptomics reveals recent CD8T cell receptor signaling in patients with coronary artery disease. Frontiers in immunology, 14, Article 1239148. https://doi.org/10.3389/fimmu.2023.1239148

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title = "Single cell transcriptomics reveals recent CD8T cell receptor signaling in patients with coronary artery disease",

abstract = "Coronary artery disease (CAD) is a major cause of death worldwide. The role of CD8+ T cells in CAD is unknown. Recent studies suggest a breakdown of tolerance in atherosclerosis, resulting in active T cell receptor (TCR) engagement with self-antigens. We hypothesized that TCR engagement would leave characteristic gene expression signatures. In a single cell RNA-sequencing analysis of CD8+ T cells from 30 patients with CAD and 30 controls we found significant enrichment of TCR signaling pathways in CAD+ subjects, suggesting recent TCR engagement. We also found significant enrichment of cytotoxic and exhaustion pathways in CAD cases compared to controls. Highly significant upregulation of TCR signaling in CAD indicates that CD8 T cells reactive to atherosclerosis antigens are prominent in the blood of CAD cases compared to controls.",

keywords = "CAD, CD8 T cells, CITE-Seq, atherosclerosis, scRNA-seq, tolerance",

author = "Shahad Iqneibi and Ryosuke Saigusa and Amir Khan and Mohammad Oliaeimotlagh and {Armstrong Suthahar}, {Sujit Silas} and Sunil Kumar and Ahmad Alimadadi and Durant, {Christopher P.} and Yanal Ghosheh and McNamara, {Coleen A.} and Hedrick, {Catherine C.} and Klaus Ley",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 Iqneibi, Saigusa, Khan, Oliaeimotlagh, Armstrong Suthahar, Kumar, Alimadadi, Durant, Ghosheh, McNamara, Hedrick and Ley.",

year = "2023",

doi = "10.3389/fimmu.2023.1239148",

language = "English (US)",

volume = "14",

journal = "Frontiers in immunology",

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AU - Iqneibi, Shahad

AU - Saigusa, Ryosuke

AU - Khan, Amir

AU - Oliaeimotlagh, Mohammad

AU - Armstrong Suthahar, Sujit Silas

AU - Kumar, Sunil

AU - Alimadadi, Ahmad

AU - Durant, Christopher P.

AU - Ghosheh, Yanal

AU - McNamara, Coleen A.

AU - Hedrick, Catherine C.

AU - Ley, Klaus

PY - 2023

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N2 - Coronary artery disease (CAD) is a major cause of death worldwide. The role of CD8+ T cells in CAD is unknown. Recent studies suggest a breakdown of tolerance in atherosclerosis, resulting in active T cell receptor (TCR) engagement with self-antigens. We hypothesized that TCR engagement would leave characteristic gene expression signatures. In a single cell RNA-sequencing analysis of CD8+ T cells from 30 patients with CAD and 30 controls we found significant enrichment of TCR signaling pathways in CAD+ subjects, suggesting recent TCR engagement. We also found significant enrichment of cytotoxic and exhaustion pathways in CAD cases compared to controls. Highly significant upregulation of TCR signaling in CAD indicates that CD8 T cells reactive to atherosclerosis antigens are prominent in the blood of CAD cases compared to controls.

AB - Coronary artery disease (CAD) is a major cause of death worldwide. The role of CD8+ T cells in CAD is unknown. Recent studies suggest a breakdown of tolerance in atherosclerosis, resulting in active T cell receptor (TCR) engagement with self-antigens. We hypothesized that TCR engagement would leave characteristic gene expression signatures. In a single cell RNA-sequencing analysis of CD8+ T cells from 30 patients with CAD and 30 controls we found significant enrichment of TCR signaling pathways in CAD+ subjects, suggesting recent TCR engagement. We also found significant enrichment of cytotoxic and exhaustion pathways in CAD cases compared to controls. Highly significant upregulation of TCR signaling in CAD indicates that CD8 T cells reactive to atherosclerosis antigens are prominent in the blood of CAD cases compared to controls.

KW - CAD

KW - CD8 T cells

KW - CITE-Seq

KW - atherosclerosis

KW - scRNA-seq

KW - tolerance

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Single cell transcriptomics reveals recent CD8T cell receptor signaling in patients with coronary artery disease

Abstract

Keywords

ASJC Scopus subject areas

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