High-Dimensional Mass Cytometry Reveals Emphysema-associated Changes in the Pulmonary Immune System
American Journal of Respiratory and Critical Care Medicine, vol. 210, pp. 1002–1016
Abstract
Abstract Rationale Chronic inflammation plays an important role in alveolar tissue damage in emphysema, but the underlying immune alterations and cellular interactions are incompletely understood. Objectives To explore disease-specific pulmonary immune cell alterations and cellular interactions in emphysema. Methods We used single-cell mass cytometry (CyTOF) to compare the immune compartment in alveolar tissue from 15 patients with severe emphysema and 5 control subjects. Imaging mass cytometry (IMC) was applied to identify altered cell–cell interactions in alveolar tissue from patients with emphysema (n = 12) compared with control subjects (n = 8). Measurements and Main Results We observed higher percentages of central memory CD4 T cells in combination with lower proportions of effector memory CD4 T cells in emphysema. In addition, proportions of cytotoxic central memory CD8 T cells and CD127+CD27+CD69− T cells were higher in emphysema, the latter potentially reflecting an influx of circulating lymphocytes into the lungs. Central memory CD8 T cells, isolated from alveolar tissue from patients with emphysema, exhibited an IFN-γ response upon anti-CD3 and anti-CD28 activation. Proportions of CD1c+ dendritic cells, expressing migratory and costimulatory markers, were higher in emphysema. Importantly, IMC enabled us to visualize increased spatial colocalization of CD1c+ dendritic cells and CD8 T cells in emphysema in situ. Conclusions Using CyTOF, we characterized the alterations of the immune cell signature in alveolar tissue from patients with chronic obstructive pulmonary disease stage III or IV emphysema versus control lung tissue. These data contribute to a better understanding of the pathogenesis of emphysema and highlight the feasibility of interrogating the immune cell signature using CyTOF and IMC in human lung tissue. Clinical trial registered with www.clinicaltrials.gov (NCT04918706).
Authors 14
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Leiden University Medical Center
Affiliation as printed
Department of Immunology
Department of Pulmonology, PulmoScience Lab, Leiden University Medical Center, Leiden, the Netherlands
Leiden University Medical Center, 4501, Immunology, Leiden, Zuid-Holland, Netherlands
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Affiliation as printed
Department of Immunology
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research of the Ministry of Education, Institute of Zoonosis and College of Veterinary Medicine, Jilin University, Changchun, China
Jilin University College of Veterinary Medicine, 623721, Key Laboratory of Zoonosis Research, Changchun, Jilin, China
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Tamim Abdelaal Aachen
Cairo University · Leiden University Medical Center · Delft University of Technology
Affiliation as printed
Department of Radiology
Pattern Recognition and Bioinformatics, Delft University of Technology, Delft, the Netherlands
Systems and Biomedical Engineering Department, Faculty of Engineering, Cairo University, Giza, Egypt; and
Cairo University, 63526, Dept of Systems and Biomedical Engineering, Giza, Egypt
Leiden University Medical Center, 4501, Radiology, Leiden, Zuid-Holland, Netherlands
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Nannan Guo Aachen
Leiden University Medical Center
Affiliation as printed
Department of Immunology
Leiden University Medical Center, 4501, Immunology, Leiden, Zuid-Holland, Netherlands
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Marieke E. IJsselstein Aachen
Leiden University Medical Center
Affiliation as printed
Department of Pathology, and
Leiden University Medical Center, 4501, Pathology, Leiden, Zuid-Holland, Netherlands
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Vincent van Unen Aachen
Leiden University Medical Center
Affiliation as printed
Department of Immunology
Leiden University Medical Center, 4501, Immunology, Leiden, Zuid-Holland, Netherlands
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Ciska Lindelauf Aachen
Leiden University Medical Center
Affiliation as printed
Department of Immunology
Leiden University Medical Center, 4501, Immunology, Leiden, Zuid-Holland, Netherlands
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Qinyue Jiang Aachen
Leiden University Medical Center
Affiliation as printed
Department of Immunology
Leiden University Medical Center, 4501, Immunology, Leiden, Zuid-Holland, Netherlands
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Yanling Xiao Aachen
Leiden University Medical Center
Affiliation as printed
Department of Immunology
Leiden University Medical Center, 4501, Immunology, Leiden, Zuid-Holland, Netherlands
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María Fernanda Pascutti Aachen
Leiden University Medical Center
Affiliation as printed
Department of Immunology
Leiden University Medical Center, 4501, Immunology, Leiden, Zuid-Holland, Netherlands
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Pieter Sicco Hiemstra Aachen Department of Pulmonology, PulmoScience Lab Department of Pulmonology, Leiden
Leiden University Medical Center
Affiliation as printed
Department of Pulmonology, PulmoScience Lab, Leiden University Medical Center, Leiden, the Netherlands
Leiden University Medical Center, 4501, Department of Pulmonology, Leiden, Zuid-Holland, Netherlands
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Frits Koning Aachen
Leiden University Medical Center
Affiliation as printed
Department of Immunology
Leiden Universitair Medisch Centrum, 4501, Immunology, Leiden, Zuid-Holland, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pulmonology, PulmoScience Lab, Leiden University Medical Center, Leiden, the Netherlands
Leiden University Medical Center, 4501, Pulmonology, Leiden, Zuid-Holland, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pulmonology, PulmoScience Lab, Leiden University Medical Center, Leiden, the Netherlands
Leiden University Medical Center, 4501, Pulmonology, Leiden, Netherlands;
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