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4 results on '"Kassiteridi, Christina"'

1. CD200 Limits Monopoiesis and Monocyte Recruitment in Atherosclerosis.

Author

Kassiteridi C, Cole JE, Griseri T, Falck-Hansen M, Goddard ME, Seneviratne AN, Green PA, Park I, Shami AG, Pattarabanjird T, Upadhye A, Taylor AM, Handa A, Channon KM, Lutgens E, McNamara CA, Williams RO, and Monaco C

Subjects
Adult, Aged, Aged, 80 and over, Animals, Antigens, CD genetics, Aorta immunology, Aorta pathology, Aortic Diseases genetics, Aortic Diseases immunology, Aortic Diseases pathology, Atherosclerosis genetics, Atherosclerosis immunology, Atherosclerosis pathology, Cells, Cultured, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease immunology, Coronary Artery Disease metabolism, Disease Models, Animal, Female, Humans, Macrophages immunology, Macrophages metabolism, Male, Mice, Inbred C57BL, Mice, Knockout, ApoE, Middle Aged, Monocytes immunology, Orexin Receptors metabolism, Phosphorylation, Plaque, Atherosclerotic, STAT1 Transcription Factor metabolism, Signal Transduction, Mice, Antigens, CD metabolism, Aorta metabolism, Aortic Diseases metabolism, Atherosclerosis metabolism, Chemotaxis, Leukocyte, Leukopoiesis, Membrane Glycoproteins metabolism, Monocytes metabolism
Abstract

[Figure: see text].

Published
2021
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2. Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity.

Author

Cole JE, Park I, Ahern DJ, Kassiteridi C, Danso Abeam D, Goddard ME, Green P, Maffia P, and Monaco C

Subjects
Animals, Aorta metabolism, Aorta pathology, Aortic Diseases genetics, Aortic Diseases metabolism, Aortic Diseases pathology, Atherosclerosis genetics, Atherosclerosis metabolism, Atherosclerosis pathology, Biomarkers metabolism, Diet, High-Fat, Disease Models, Animal, Mice, Knockout, ApoE, Myeloid Cells metabolism, Myeloid Cells pathology, Phenotype, Plaque, Atherosclerotic, Aorta immunology, Aortic Diseases immunology, Atherosclerosis immunology, Cell Separation methods, Flow Cytometry, Immunophenotyping methods, Myeloid Cells immunology, Spectrophotometry, Atomic
Abstract

Aims: Atherosclerosis is characterized 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 cell (ILC) 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 toward inflammatory monocyte-macrophage populations rather than resident macrophage phenotypes and cDC2 during atherogenesis.

Published
2018
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3. Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity

Author

Cole, Jennifer E., Park, Inhye, Ahern, David, Kassiteridi, Christina, Danso Abeam, Dina, Goddard, Michael, Green, Patricia, Maffia, Pasquale, Monaco, Claudia, Cole, Jennifer E., Park, Inhye, Ahern, David J., Kassiteridi, Christina, Abeam, Dina Danso, Goddard, Michael E., Green, Patricia, Maffia, Pasquale, and Monaco, Claudia

Subjects
Mice, Knockout, ApoE, Macrophage, Physiology, Aortic Diseases, Cell Separation, Antigen-Antibody Complex, Diet, High-Fat, Immunophenotyping, Mice, Vascular, Physiology (medical), Animals, Myeloid Cells, Aorta, Immunity and Inflammation, Immune cell, Spectrophotometry, Atomic, Macrophages, Immune cells, Censuses, Original Articles, Cytometry by time of flight, Flow Cytometry, Atherosclerosis, Plaque, Atherosclerotic, Disease Models, Animal, Editor's Choice, Phenotype, Atherosclerosi, Cardiology and Cardiovascular Medicine, Biomarkers
Abstract

Aims: \ud 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.\ud \ud Methods and Results: \ud 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.\ud \ud Conclusions: \ud 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.

Published
2018

4. Interferon regulatory factor 5 controls necrotic core formation in atherosclerotic lesions by impairing efferocytosis

Author

Seneviratne, Anusha N., Edsfeldt, Andreas, Cole, Jennifer E., Kassiteridi, Christina, Swart, Maarten, Park, Inhye, Green, Patricia, Khoyratty, Tariq, Saliba, David, Goddard, Michael E., Sansom, Stephen N., Goncalves, Isabel, Krams, Rob, Udalova, Irina A., Monaco, Claudia, and British Heart Foundation

Subjects
Bone Marrow Cells, 1102 Cardiovascular Medicine And Haematology, Mice, Necrosis, Apolipoproteins E, Phagocytosis, Original Research Articles, IRF5, Animals, Aorta, Cells, Cultured, Mice, Knockout, efferocytosis, CD11c, Integrin beta3, 1103 Clinical Sciences, Immunohistochemistry, CD11c Antigen, macrophages, Mice, Inbred C57BL, 1117 Public Health And Health Services, Cardiovascular System & Hematology, Interferon Regulatory Factors, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Lymph Nodes, atherosclerosis, Shear Strength
Abstract

Supplemental Digital Content is available in the text., Background: Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis) promotes lesion growth and establishment of a necrotic core. The transcription factor interferon regulatory factor (IRF)-5 is an important modulator of myeloid function and programming. We sought to investigate whether IRF5 affects the formation and phenotype of atherosclerotic lesions. Methods: We investigated the role of IRF5 in atherosclerosis in 2 complementary models. First, atherosclerotic lesion development in hyperlipidemic apolipoprotein E-deficient (ApoE-/-) mice and ApoE-/- mice with a genetic deletion of IRF5 (ApoE-/-Irf5-/-) was compared and then lesion development was assessed in a model of shear stress-modulated vulnerable plaque formation. Results: Both lesion and necrotic core size were significantly reduced in ApoE-/-Irf5-/- mice compared with IRF5-competent ApoE-/- mice. Necrotic core size was also reduced in the model of shear stress-modulated vulnerable plaque formation. A significant loss of CD11c+ macrophages was evident in ApoE-/-Irf5-/- mice in the aorta, draining lymph nodes, and bone marrow cell cultures, indicating that IRF5 maintains CD11c+ macrophages in atherosclerosis. Moreover, we revealed that the CD11c gene is a direct target of IRF5 in macrophages. In the absence of IRF5, CD11c- macrophages displayed a significant increase in expression of the efferocytosis-regulating integrin-β3 and its ligand milk fat globule-epidermal growth factor 8 protein and enhanced efferocytosis in vitro and in situ. Conclusions: IRF5 is detrimental in atherosclerosis by promoting the maintenance of proinflammatory CD11c+ macrophages within lesions and controlling the expansion of the necrotic core by impairing efferocytosis.

Published
2017

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