Detailed cellular and spatial characterization of chronic lung allograft dysfunction using imaging mass cytometry.
Benjamin Renaud-Picard1, Sajad Moshkelgosha2, Gregory Berra3
1Latner Thoracic Research Laboratories, Toronto General Hospital Research Institute, Toronto, Ontario, Canada; Toronto Lung Transplant Program, Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada; INSERM Unité mixte de recherche 1260, Regenerative Nanomedicine, University of Strasbourg, Strasbourg, France.
Summary
Chronic lung allograft dysfunction (CLAD) after lung transplants is a major survival barrier. Imaging mass cytometry revealed distinct cellular changes in CLAD, offering insights into bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS).
Area of Science:
- Immunology
- Transplantation Biology
- Cellular Pathology
Background:
- Long-term survival post-lung transplantation is significantly limited by chronic lung allograft dysfunction (CLAD).
- CLAD presents with two primary phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS).
Purpose of the Study:
- To investigate the cellular and structural characteristics of CLAD lung allografts using imaging mass cytometry (IMC).
- To identify distinct cellular profiles associated with BOS and RAS phenotypes of CLAD.
Main Methods:
- Utilized IMC, a high-dimensional tissue imaging system, for multiparametric, single-cell level analysis.
- Analyzed lung tissue samples from four BOS, four RAS, and four control subjects.
- Employed 35 heavy metal-tagged antibodies to assess structural and immune proteins in situ.
Main Results:
- Identified 50 distinct immune and non-immune cell clusters.
- Observed significantly reduced club cells in CLAD allografts.
- Found an increased prevalence of Ki67-high basal cells near memory T cells in RAS, and more memory CD8+ T cells in CLAD overall, with regulatory T cells prominent in RAS.
Conclusions:
- IMC is a powerful technology for detailed cellular analysis within intact organ structures.
- The study provides novel insights into the cellular mechanisms underlying CLAD, potentially differentiating BOS and RAS.
- Findings may guide future therapeutic strategies for improving lung allograft survival.
