1. Perirenal Adipose Tissue Displays an Age-Dependent Inflammatory Signature Associated With Early Graft Dysfunction of Marginal Kidney Transplants
- Author
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Romain Boissier, Pauline François, Bastien Gondran Tellier, Maité Meunier, Luc Lyonnet, Stephanie Simoncini, Jeremy Magalon, Tristan Legris, Laurent Arnaud, Laurent Giraudo, Françoise Dignat George, Gilles Karsenty, Stéphane Burtey, Eric Lechevallier, Florence Sabatier, Pascale Paul, Lucas, Nelly, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Aix Marseille Université (AMU), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Centre d'Investigation Clinique [Hôpital de la Conception - APHM] (CIC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), and Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)
- Subjects
Male ,0301 basic medicine ,Aging ,Pathology ,Chemokine CXCL1 ,Interleukin-1beta ,Cell ,Transplants ,Adipose tissue ,Kidney ,Transcriptome ,0302 clinical medicine ,Cell Movement ,Immunology and Allergy ,Prospective Studies ,Kidney transplantation ,Original Research ,natural killer cells ,Neovascularization, Pathologic ,Middle Aged ,Stromal vascular fraction ,Tissue Donors ,Killer Cells, Natural ,CXCL1 ,medicine.anatomical_structure ,Adipose Tissue ,marginal kidney donors ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,endothelial inflammation ,Adult ,lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,Stromal cell ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Immunology ,kidney transplantation ,03 medical and health sciences ,medicine ,Humans ,perirenal adipose tissue ,Aged ,Inflammation ,kidney allograft dysfunction ,business.industry ,Macrophages ,medicine.disease ,030104 developmental biology ,Primary Graft Dysfunction ,lcsh:RC581-607 ,business ,030215 immunology - Abstract
International audience; Background: Better understanding of the contribution of donor aging and comorbidity factors of expanded criteria donors (ECD) to the clinical outcome of a transplant is a challenge in kidney transplantation. We investigated whether the features of donor-derived stromal vascular fraction of perirenal adipose tissue (PRAT-SVF) could be indicative of the deleterious impact of the ECD microenvironment on a renal transplant. Methods: A comparative analysis of cellular components, transcriptomic and vasculogenic profiles was performed in PRAT-SVF obtained from 22 optimal donors and 31 ECD deceased donors. We then investigated whether these parameters could be associated with donor aging and early allograft dysfunction.Results: When compared with the PRAT-SVF of non-ECD donors, ECD PRAT-SVF displayed a lower proportion of stromal cells, a higher proportion of inflammatory NK cells. The global RNA sequencing approach indicated a differential molecular signature in the PRAT-SVF of ECD donors characterized by the over-expression of CXCL1 and IL1-beta inflammatory transcripts. The vasculogenic activity of PRAT-SVF was highly variable but was not significantly affected in marginal donors. Periorgan recruitment of monocytes/macrophages and NK cells in PRAT-SVF was associated with donor aging. The presence of NK cell infiltrates was associated with lower PRAT-SVF angiogenic activity and with early allograft dysfunction evaluated on day 7 and at 1 month post-transplant. Conclusions: Our results indicate that human NK cell subsets are differentially recruited in the periorgan environment of aging kidney transplants. We provide novel evidence that PRAT-SVF represents a non-invasive and timely source of donor material with potential value to assess inflammatory features that impact organ quality and function.
- Published
- 2020