AUTHOR=Kaes Janne , Hooft Charlotte , Jin Xin , Heigl Tobias , Liu Hengshuo , Pollenus Emilie , Prenen Fran , Beeckmans Hanne , Kerckhof Pieterjan , Vanstapel Arno , Van Slambrouck Jan , Mercurio Martina , Zapata-Ortega Marta , Aerts Gitte , Geudens Vincent , Vermaut Astrid , Vanvuchelen Lise , Somers Anse , Verbeylen Lara , Vanluyten Cedric , Barbarossa Annalisa , Mohamady Yousry , Özsoy Balin , Zajacova Andrea , Tielemans Birger , Yildirim Ali Onder , Bos Saskia , De Sadeleer Laurens , Godinas Laurent , Rojas Quintero Joselyn , Polverino Francesca , Van den Steen Philippe E. , Ceulemans Laurens J. , Vos Robin , Vanaudenaerde Bart M. 
  
TITLE=Blood vessels as primary site of rejection in murine lung transplantation
  
JOURNAL=Transplant International
  
VOLUME=Volume 39 - 2026
  
YEAR=2026
  
URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2026.16293
  
DOI=10.3389/ti.2026.16293
  
ISSN=1432-2277
  
ABSTRACT=Survival after lung transplantation lags that of other solid organ transplants. Long-term survival is hampered primarily due to chronic lung allograft dysfunction (CLAD) development. It remains elusive how (chronic) rejection is organized within the lung graft over time post-transplant. Using a model of orthotopic left lung transplantation in major mismatched mouse strains with daily immunosuppression, we aimed to study the spatiotemporal dynamics of (chronic) rejection, using micro-computed tomography imaging, flow cytometric analyses and spatial proteomics. Endothelial cells demonstrated early activation and destruction (day 7 post-transplant). The accompanying early inflammation at the vascular compartment, progressed towards aberrant tissue repair resulting in irreversible bronchovascular fibrosis and chronic graft dysfunction. We provide new insights in the spatiotemporal dynamics of (chronic) rejection with a vascular-oriented onset that may have future implications for diagnosis and treatment in clinical lung transplantation.