Single-cell immune landscape of human atherosclerotic plaques

Dawn M. Fernandez, Adeeb H. Rahman, Nicolas F. Fernandez, Aleksey Chudnovskiy, El ad David Amir, Letizia Amadori, Nayaab S. Khan, Christine K. Wong, Roza Shamailova, Christopher A. Hill, Zichen Wang, Romain Remark, Jennifer R. Li, Christian Pina, Christopher Faries, Ahmed J. Awad, Noah Moss, Johan L.M. Bjorkegren, Seunghee Kim-Schulze, Sacha GnjaticAvi Ma’ayan, J. Mocco, Peter Faries, Miriam Merad, Chiara Giannarelli

Research output: Contribution to journalArticlepeer-review

449 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1576-1588
Number of pages13
JournalNature Medicine
Volume25
Issue number10
DOIs
StatePublished - 1 Oct 2019

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