Imaging Mass Cytometry for Detailed Cellular and Spatial Characterization of Chronic Lung Allograft Dysfunction (CLAD)
نویسندگان
چکیده
PurposeCLAD, the main limitation to long-term survival after a lung transplantation (LTx), has two phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft (RAS). There is great need for better characterization of cells within tissue. We aimed assess CLAD allografts using imaging mass cytometry (IMC), high dimensional tissue system allowing comprehensive multiparametric in situ exploration microenvironments at single cell level, heavy metal-tagged antibodies.MethodsExplanted was obtained time retransplantation from 4 BOS patients, RAS control donor lungs. Paraffin-embedded sectioned stained with 35 heavy-metal-tagged antibodies selected identify structural immune proteins interest. For each sample, three 1 mm2 regions interest, centered on an airway, were ablated data analyzed MCD viewer HistoCAT software.ResultsTo specific subsets identified by combinations markers, we used tSNE create 2D representation organised 50 non-immune clusters according similarity their antibody-binding 35-dimensional space (Figure 1A). present several key examples our findings: lungs had significantly reduced club 1B-D, H) trend towards basal I). A Ki67-high population mostly samples I-J) close proximity memory T (neighborhood analysis not shown, Figure 1L). Memory CD8+ more frequent 1E-G, K) prominent regulatory 1E-G).ConclusionIMC allowed us distinct cytotoxic IMC powerful technology detailed cellular intact organ structures that may shed further light mechanisms. CLAD, antibodies. Explanted software. To 1E-G).
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Affiliations: Clinique Universitaire de Pneumologie, Pôle de Cancérologie, Médecine Aiguë et Communautaire, CHU Grenoble, Inserm1055, Grenoble, Université Joseph Fourier, Grenoble, European Institute for Systems Biology and Medicine, EISBM, Lyon, Institut du Thorax, Inserm UMR1087, CNRS UMR629, Service de Pneumologie, CHU de Nantes DHU2020, Nantes, Université de Nantes, Nantes, Université Josep...
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ژورنال
عنوان ژورنال: Journal of Heart and Lung Transplantation
سال: 2022
ISSN: ['1053-2498', '1557-3117']
DOI: https://doi.org/10.1016/j.healun.2022.01.246