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Kaes, J.* ; Pollenus, E.* ; Hooft, C.* ; Liu, H. ; Aelbrecht, C.* ; Cambier, S.* ; Jin, X.* ; Van Slambrouck, J.* ; Beeckmans, H.* ; Kerckhof, P.* ; Velde, G.V.* ; Van Raemdonck, D.* ; Yildirim, A.Ö. ; Van den Steen, P.E.* ; Vos, R.* ; Ceulemans, L.J.* ; Vanaudenaerde, B.M.*

The immunopathology of pulmonary rejection after murine lung transplantation.

Cells 13:241 (2024)
DOI PMC
Creative Commons Lizenzvertrag
To improve outcomes following lung transplantation, it is essential to understand the immunological mechanisms that result in chronic graft failure. The associated clinical syndrome is termed chronic lung allograft dysfunction (CLAD), which is known to be induced by alloimmune-dependent (i.e., rejection) and alloimmune-independent factors (e.g., infections, reflux and environmental factors). We aimed to explore the alloimmune-related mechanism, i.e., pulmonary rejection. In this study, we use a murine orthotopic left lung transplant model using isografts and allografts (C57BL/6 or BALB/c as donors to C57BL/6 recipients), with daily immunosuppression (10 mg/kg cyclosporin A and 1.6 mg/kg methylprednisolone). Serial sacrifice was performed at days 1, 7 and 35 post-transplantation (n = 6 at each time point for each group). Left transplanted lungs were harvested, a single-cell suspension was made and absolute numbers of immune cells were quantified using multicolor flow cytometry. The rejection process followed the principles of a classic immune response, including innate but mainly adaptive immune cells. At day 7 following transplantation, the numbers of interstitial macrophages, monocytes, dendritic cells, NK cells, NKT cells, CD4+ T cells and CD8+ T and B cells were increased in allografts compared with isografts. Only dendritic cells and CD4+ T cells remained elevated at day 35 in allografts. Our study provides insights into the immunological mechanisms of true pulmonary rejection after murine lung transplantation. These results might be important in further research on diagnostic evaluation and treatment for CLAD.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Chronic Lung Allograft Dysfunction (clad) ; Immunology ; Lung Transplantation ; Murine Orthotopic Left Lung Transplantation ; Pulmonary Rejection; Bronchoalveolar Lavage; Allograft Dysfunction; Phenotypes; Mechanisms; Update; Model
ISSN (print) / ISBN 2073-4409
e-ISSN 2073-4409
Journal Cells
Quellenangaben Volume: 13, Issue: 3, Pages: , Article Number: 241 Supplement: ,
Publisher MDPI
Publishing Place Basel
Non-patent literature Publications
Grants FWO