Preconditioning donors with corticosteroids improves the early lung graft immunity | Preconditioning donors with corticosteroids improves the early lung graft immunity: lung immunity upon donor preconditioning with corticosteroids
2025
Schwartz-Cornil, Isabelle | Pascale, Florentina | Jouneau, Luc | Huriet, Maxime | Estephan, Jérôme | Bourge, Mickaël | Richard, Christophe | Gelin, Valerie | Bevilacqua, Claudia | Rivière, Julie | Vu Manh, Thien-Phong | Djebbour, Maxime | Premachandra, Antoine | Gouin, Carla | de Wolf, Julien | Mimbimi, Chloé | Magnan, Antoine | Roux, Antoine | Grassin Delyle, Stanislas | Devillier, Philippe | Descamps, Delphyne | Bertho, Nicolas | Jacqmin, Sébastien | Le Guen, Morgan | Sage, Édouard | Glorion, Matthieu | Virologie et Immunologie Moléculaires (VIM (UR 0892)) ; Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Hôpital Foch [Suresnes] | Institut de Biologie Intégrative de la Cellule (I2BC) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) | Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED) ; École nationale vétérinaire d'Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Génétique Animale et Biologie Intégrative (GABI) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Centre d'Immunologie de Marseille - Luminy (CIML) ; Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Service de pneumologie [Hôpital Foch] ; Hôpital Foch [Suresnes] | Infection et inflammation (2I) ; Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Laboratory of Research in Respiratory Pharmacology, Exhalomics Facility, Foch Hospital, University Paris-Saclay, Suresnes, France. | Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR) ; École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Chirurgie thoracique et transplantation pulmonaire [Suresnes] (CT2P - Hôpital Foch) ; Hôpital Foch [Suresnes] | The project was supported by i) the “Ile-de-France region” within the Pulmonary vulnerability Major Interest Question project (reference 230080000), ii) the Versailles-Saint-Quentin-en-Yvelines University/Paris-Saclay University, iii) Association chirurgicale pour le développement et l’amélioration des techniques de dépistage et de traitement des maladie cardio-vasculaire, iv) the Chaire Universitaire de Transplantation of the Versailles-Saint-Quentin-en-Yvelines University and Foch Hospital, v) the Foch foundation, vi) the Association Gregory Lemarchal and the association Vaincre la Mucoviscidose (project number RF20220503016), vii) National Research Institute for Agriculture, Food and Environment support, viii) Assistance Publique et Hôpitaux de Paris for M.D. financial support ("année recherche") . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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: Donor preconditioning - compared to recipient’s treatment alone - reduced the presence of CD3pos T-cell 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 upon 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.
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