American journal of respiratory and critical care medicine, 27 4 2024 High-Dimensional Mass Cytometry Reveals Emphysema-associated Changes in the Pulmonary Immune System. Jia L, Li N, Abdelaal TRM, Guo N, IJsselstein ME, van Unen V, Lindelauf C, Jiang Q, Xiao Y, Pascutti MF, Hiemstra PS, Koning F, Stolk J, Khedoe PPSJ
Rationale
Chronic inflammation plays an important role in alveolar tissue damage in emphysema, but the underlying immune alterations and cellular interactions are incompletely understood.
Objective
To explore disease-specific pulmonary immune cell alterations and cellular interactions in emphysema.
Methods
We 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 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 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.
Conclusion
Using 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.
