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- Alma Zernecke
- From the Institute of Experimental Biomedicine (A.Z., C.C.), University Hospital Würzburg, Germany
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- Holger Winkels
- Heart Center, University Hospital Cologne, Germany (H.W.)
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- Clément Cochain
- From the Institute of Experimental Biomedicine (A.Z., C.C.), University Hospital Würzburg, Germany
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- Jesse W. Williams
- Department of Integrative Biology and Physiology (J.W.W.), University of Minnesota Medical School, Minneapolis
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- Dennis Wolf
- Department of Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (D.W.)
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- Oliver Soehnlein
- Institute for Cardiovascular Prevention, Klinikum LMU Munich, Germany (O.S.)
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- Clint S. Robbins
- Department of Laboratory Medicine and Pathobiology (C.S.R.), University of Toronto, ON, Canada
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- Claudia Monaco
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, United Kingdom (C.M., I.P.)
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- Inhye Park
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, United Kingdom (C.M., I.P.)
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- Coleen A. McNamara
- Robert M. Berne Cardiovascular Research Center (C.A.M.), University of Virginia School of Medicine, Charlottesville
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- Christoph J. Binder
- Department of Laboratory Medicine, Medical University of Vienna, Austria (C.J.B.)
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- Myron I. Cybulsky
- Department of Laboratory Medicine and Pathobiology (M.I.C., C.A.S.), University of Toronto, ON, Canada
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- Corey A. Scipione
- Department of Laboratory Medicine and Pathobiology (M.I.C., C.A.S.), University of Toronto, ON, Canada
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- Catherine C. Hedrick
- La Jolla Institute for Immunology, CA (C.C.H., Y.G., H.Q.D., K.L.)
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- Elena V. Galkina
- Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk (E.V.G.)
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- Tin Kyaw
- Vascular Biology and Atherosclerosis Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia (T.K.)
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- Yanal Ghosheh
- La Jolla Institute for Immunology, CA (C.C.H., Y.G., H.Q.D., K.L.)
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- Huy Q. Dinh
- La Jolla Institute for Immunology, CA (C.C.H., Y.G., H.Q.D., K.L.)
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- Klaus Ley
- La Jolla Institute for Immunology, CA (C.C.H., Y.G., H.Q.D., K.L.)
抄録
<jats:p> The diverse leukocyte infiltrate in atherosclerotic mouse aortas was recently analyzed in 9 single-cell RNA sequencing and 2 mass cytometry studies. In a comprehensive meta-analysis, we confirm 4 known macrophage subsets—resident, inflammatory, interferon-inducible cell, and Trem2 (triggering receptor expressed on myeloid cells-2) foamy macrophages—and identify a new macrophage subset resembling cavity macrophages. We also find that monocytes, neutrophils, dendritic cells, natural killer cells, innate lymphoid cells-2, and CD (cluster of differentiation)-8 T cells form prominent and separate immune cell populations in atherosclerotic aortas. Many CD4 T cells express IL (interleukin)-17 and the chemokine receptor CXCR (C-X-C chemokine receptor)-6. A small number of regulatory T cells and T helper 1 cells is also identified. Immature and naive T cells are present in both healthy and atherosclerotic aortas. Our meta-analysis overcomes limitations of individual studies that, because of their experimental approach, over- or underrepresent certain cell populations. Mass cytometry studies demonstrate that cell surface phenotype provides valuable information beyond the cell transcriptomes. The present analysis helps resolve some long-standing controversies in the field. First, Trem2 <jats:sup>+</jats:sup> foamy macrophages are not proinflammatory but interferon-inducible cell and inflammatory macrophages are. Second, about half of all foam cells are smooth muscle cell-derived, retaining smooth muscle cell transcripts rather than transdifferentiating to macrophages. Third, <jats:italic>Pf4</jats:italic> , which had been considered specific for platelets and megakaryocytes, is also prominently expressed in the main population of resident vascular macrophages. Fourth, a new type of resident macrophage shares transcripts with cavity macrophages. Finally, the discovery of a prominent innate lymphoid cell-2 cluster links the single-cell RNA sequencing work to recent flow cytometry data suggesting a strong atheroprotective role of innate lymphoid cells-2. This resolves apparent discrepancies regarding the role of T helper 2 cells in atherosclerosis based on studies that predated the discovery of innate lymphoid cells-2 cells. </jats:p>
収録刊行物
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- Circulation Research
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Circulation Research 127 (3), 402-426, 2020-07-17
Ovid Technologies (Wolters Kluwer Health)