AUTHOR=Schwartz-Cornil Isabelle , Pascale Florentina , Jouneau Luc , Huriet Maxime , Estephan Jérôme , Bourge Mickael , Richard Christophe , Gelin Valérie , 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 Edouard , Glorion Matthieu 

TITLE=Preconditioning donors with corticosteroids improves early lung graft immunity

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1668591

DOI=10.3389/fimmu.2025.1668591

ISSN=1664-3224

ABSTRACT=BackgroundPreclinical 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.MethodWe 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.ResultsDonor preconditioning - compared to recipient’s treatment alone - reduced the presence of CD3pos 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.ConclusionOur 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.