• Am. J. Respir. Crit. Care Med. · Mar 2024

    High-Dimensional Mass Cytometry Reveals Emphysema-associated Changes in the Pulmonary Immune System.

    • Li Jia, Na Li, Tamim R M Abdelaal, Nannan Guo, Marieke E IJsselstein, Vincent van Unen, Ciska Lindelauf, Qinyue Jiang, Yanling Xiao, M Fernanda Pascutti, Pieter S Hiemstra, Frits Koning, Jan Stolk, and KhedoeP Padmini S JPPSJ0000-0002-0798-014XLeiden University Medical Center, 4501, Pulmonology, Leiden, Netherlands; p.p.s.j.khedoe@lumc.nl..
    • Leiden University Medical Center, 4501, Immunology, Leiden, Zuid-Holland, Netherlands.
    • Am. J. Respir. Crit. Care Med. 2024 Mar 27.

    RationaleChronic inflammation plays an important role in alveolar tissue damage in emphysema, but the underlying immune alterations and cellular interactions are incompletely understood.ObjectiveTo explore disease-specific pulmonary immune cell alterations and cellular interactions in emphysema.MethodsWe used single-cell mass cytometry to compare the immune compartment in alveolar tissue from 15 patients with severe emphysema and 5 controls. Imaging mass cytometry (IMC) was applied to identify altered cell-cell interactions in alveolar tissue from emphysema patients (n=12) compared to controls (n=8).Measurements And Main ResultsWe 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 emphysema patients exhibited an IFN-γ-response upon anti-CD3/anti-CD28 activation. Proportions of CD1c+ dendritic cells (DC), expressing migratory and costimulatory markers, were higher in emphysema. Importantly, IMC enabled us to visualize increased spatial colocalization of CD1c+ DC and CD8 T cells in emphysema in situ.ConclusionUsing single-cell CyTOF, we characterized the alterations of the immune cell signature in alveolar tissue from patients with COPD stage III/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 single-cell and IMC in human lung tissue.

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