Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity

Cole, J. E., Park, I., Ahern, D., Kassiteridi, C., Danso Abeam, D., Goddard, M., Green, P., Maffia, P. and Monaco, C. (2018) Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity. Cardiovascular Research, 114(10), pp. 1360-1371. (doi:10.1093/cvr/cvy109) (PMID:29726984) (PMCID:PMC6054192)

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Abstract

Aims: Atherosclerosis is characterised by the abundant infiltration of myeloid cells starting at early stages of disease. Myeloid cells are key players in vascular immunity during atherogenesis. However, the subsets of vascular myeloid cells have eluded resolution due to shared marker expression and atypical heterogeneity in vascular tissues. We applied the high-dimensionality of mass cytometry to the study of myeloid cell subsets in atherosclerosis. Methods and Results: Apolipoprotein E-deficient (ApoE-/-) mice were fed a chow or a high fat (western) diet for 12 weeks. Single cell aortic preparations were probed with a panel of 35 metal-conjugated antibodies using Cytometry by time of flight (CyTOF). Clustering of marker expression on live CD45+ cells from the aortas of ApoE-/- mice identified 13 broad populations of leucocytes. Monocyte, macrophage, type 1 and type 2 conventional dendritic cell (cDC1 and cDC2), plasmacytoid dendritic cell (pDC), neutrophil, eosinophil, B cell, CD4+ and CD8+ T cell, γδ T cell, natural killer (NK) cell and innate lymphoid (ILC) cell populations accounted for approximately 95% of the live CD45+ aortic cells. Automated clustering algorithms applied to the Lin-CD11blo-hi cells revealed 20 clusters of myeloid cells. Comparison between chow and high fat fed animals revealed increases in monocytes (both Ly6C+ and Ly6C-), pDC and a CD11c+ macrophage subset with high fat feeding. Concomitantly, the proportions of CD206+ CD169+ subsets of macrophages were significantly reduced as were cDC2. Conclusions: A CyTOF-based comprehensive mapping of the immune cell subsets within atherosclerotic aortas from ApoE-/- mice offers tools for myeloid cell discrimination within the vascular compartment and it reveals that high fat feeding skews the myeloid cell repertoire towards inflammatory monocyte-macrophage populations rather than resident macrophage phenotypes and cDC2 during atherogenesis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maffia, Dr Pasquale
Authors: Cole, J. E., Park, I., Ahern, D., Kassiteridi, C., Danso Abeam, D., Goddard, M., Green, P., Maffia, P., and Monaco, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cardiovascular Research
Publisher:Oxford University Press
ISSN:0008-6363
ISSN (Online):1755-3245
Published Online:02 May 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Cardiovascular Research 114(10): 1360-1371
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
614711Defining innate and adaptive immune functions of plasmacytoid dendritic cells in atherosclerosis.Pasquale MaffiaBritish Heart Foundation (BHF)PG/12/81/29897III -IMMUNOLOGY
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES