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Single-cell immune landscape of human atherosclerotic plaques.

Authors
  • Fernandez, Dawn M1
  • Rahman, Adeeb H2, 3, 4
  • Fernandez, Nicolas F3
  • Chudnovskiy, Aleksey2
  • Amir, El-Ad David3
  • Amadori, Letizia4
  • Khan, Nayaab S1
  • Wong, Christine K1
  • Shamailova, Roza1
  • Hill, Christopher A1
  • Wang, Zichen5
  • Remark, Romain2, 6
  • Li, Jennifer R7
  • Pina, Christian7
  • Faries, Christopher7
  • Awad, Ahmed J8, 9
  • Moss, Noah1
  • Bjorkegren, Johan L M4, 10
  • Kim-Schulze, Seunghee2, 3, 11
  • Gnjatic, Sacha2, 3, 12
  • And 5 more
  • 1 Cardiovascular Research Center, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 2 The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 3 Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 4 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 5 Mount Sinai Center for Bioinformatics, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 6 Innate Pharma, Marseille, France. , (France)
  • 7 Department of Surgery, Vascular Division, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 8 Cerebrovascular Center, Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 9 Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA.
  • 10 Integrated Cardio MetabolicCentre, Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden. , (Sweden)
  • 11 Hematology and Medical Oncology Division, The Tish Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 12 Department of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 13 Cardiovascular Research Center, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected]
  • 14 The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected]
  • 15 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected]
Type
Published Article
Journal
Nature medicine
Publication Date
Oct 01, 2019
Volume
25
Issue
10
Pages
1576–1588
Identifiers
DOI: 10.1038/s41591-019-0590-4
PMID: 31591603
Source
Medline
Language
English
License
Unknown

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.

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