Single-cell immune landscape of human atherosclerotic plaques

By Dawn M. Fernandez, Adeeb H. Rahman, Nicolas F. Fernandez, A. Chudnovskiy, E. Amir, L. Amadori, N. Khan, Christine K. Wong, Roza Shamailova, C. Hill and 15 more. Nature Medicine, 2019

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Atherosclerosis is driven by multifaceted contributions of the immune system within the circulation and at vascular focal sites. However, specific characteristics of dysregulated immune cells within atherosclerotic lesions that lead to clinical events such as ischemic stroke or myocardial infarction are poorly understood. Here, using single-cell proteomic and transcriptomic analyses, we uncovered distinct features of both T cells and macrophages in carotid artery plaques of patients with clinically symptomatic disease (recent stroke or transient ischemic attack) compared to asymptomatic disease (no recent stroke). Plaques from symptomatic patients were characterized by a distinct subset of CD4+ T cells and by T cells that were activated and differentiated. Moreover, some T cell subsets in these plaques presented markers of T cell exhaustion. Additionally, macrophages from these plaques contained alternatively activated phenotypes, including subsets associated with plaque vulnerability. In plaques from asymptomatic patients, T cells and macrophages were activated and displayed evidence of interleukin-1β signaling. The identification of specific features of innate and adaptive immune cells in plaques that are associated with cerebrovascular events may enable the design of more precisely tailored cardiovascular immunotherapies. Single-cell proteomic and transcriptional profiling of atherosclerotic lesions from human carotid arteries reveals specific features of lesional T cells and macrophages associated with symptomatic disease.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2c992eb70a6620c1e3dbc4e9f1b6459f9fe6d4d3

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Citations in the corpus

Inflammation and atherosclerosis: signaling pathways and therapeutic intervention (2022, background): “Dysregulation of immune cells in the plaques has been recently uncovered by using single-cell transcriptomic and proteomic analyses.(11) The plaques in symptomatic patients exhibited the characterization of a distinct CD4 T-cell subset and T cells to be activated and differentiated, whereas in the p”
Atherosclerosis: Recent developments (2022, result): “Somewhat in contrast, it was shown that carotid plaques from symptomatic patients were characterized by a distinct subset of CD4+ T cells that were activated and differentiated (Fernandez et al., 2019).”
Deciphering cell–cell interactions and communication from gene expression (2020, methodology): “Although this method can be applied to bulk data, microdissected or single-cell data sets are preferred as they capture the full heterogeneity of expression across cells 19,48,49,55,60,62 , resulting in clearer differences in expression 92 .”