Year: 2025
Type: article
Abstract: Background: Preclinical studies have recently revealed the critical role of innate immunity in determining lung transplantation outcomes. Although the International Society for Heart and Lung Transplantation recommends high-dose corticosteroid administration to donors, this practice is inconsistently applied worldwide. Investigating its impact on the donor lung's innate immune response - an unexplored area - could provide valuable evidence to support adoption of donor preconditioning with corticosteroids, beyond their traditional administration to recipients. Method: We used a cross-circulatory pig platform that consists of a donor lung placed extracorporeally and connected to the circulation of a recipient pig whose leukocytes are fluorescently labeled. Results: T-cells in the graft from both the donor and recipient, and enhanced the anti-inflammatory profile of alveolar macrophages, at least during the first 10 hours of donor-recipient interaction. The alveolar macrophages isolated from corticosteroid-preconditioned pig lungs exhibited decreased gene expression of T-cell-attracting chemokines during the 10-hour reperfusion period, correlating with the reduced T-cell infiltration. Similarly, human lung macrophages showed lower expression of these T-cell-attracting chemokines and higher anti-inflammatory profiles with corticosteroid treatment. Conclusion: Our results show that the early immune status of lung grafts is improved by treating donors with corticosteroids through macrophage-targeted mechanisms. This finding provides an immunological rationale for expanding the implementation of donor preconditioning with corticosteroids.
Source: Frontiers in Immunology
Authors: Isabelle Schwartz-Cornil, Florentina Pascale, Luc Jouneau, Maxime Huriet, Jérôme Estephan, Mickael Bourge, Christophe Richard, Valérie Gelin, Claudia Bevilacqua, Julie Rivière, Thien-Phong Vu Manh, Maxime Djebbour, Antoine Premachandra, Carla Gouin, Julien De Wolf, Chloé Mimbimi, Antoine Magnan, Antoine Roux, Stanislas Grassin-Delyle, Philippe Devillier, Delphyne Descamps, Nicolas Bertho, Sébastien Jacqmin, Morgan Le Guen, Edouard Sage, Matthieu Glorion
Institutions: Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Virologie et Immunologie Moléculaires, Hôpital Foch, Centre National de la Recherche Scientifique, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Intégrative de la Cellule, CEA Paris-Saclay, Biologie de la Reproduction, Environnement, Epigénétique et Développement, AgroParisTech, Génétique Animale et Biologie Intégrative, Microbiologie de l’alimentation au service de la santé, Inserm, Aix-Marseille Université, Centre d’Immunologie de Marseille-Luminy, Infection et inflammation, Oniris, Biologie, Epidémiologie et Analyse de Risque en Santé Animale
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W4415057985