Missing self triggers NK cell-mediated chronic vascular rejection of solid organ transplants

Alice Koenig, Chien-Chia Chen, Antoine Marçais, Thomas Barba, Virginie Mathias, Antoine Sicard, Maud Rabeyrin, Maud Racapé, Jean-Paul Duong- Van-Huyen, Patrick Bruneval, Alexandre Loupy, Sébastien Dussurgey, Stéphanie Ducreux, Vannary Meas-Yedid, Jean-Christophe Olivo-Marin, Héléna Paidassi, Romain Guillemain, Jean-Luc Taupin, Jasper Callemeyn, Emmanuel Morelon, Antonino Nicoletti, Béatrice Charreau, Valérie Dubois, Maarten Naesens, Thierry Walzer, Thierry Defrance and Olivier Thaunat ()
Additional contact information
Alice Koenig: Univ. Lyon
Chien-Chia Chen: Univ. Lyon
Antoine Marçais: Univ. Lyon
Thomas Barba: Univ. Lyon
Virginie Mathias: Univ. Lyon
Antoine Sicard: Univ. Lyon
Maud Rabeyrin: Department of Pathology
Maud Racapé: Paris Descartes University
Jean-Paul Duong- Van-Huyen: Paris Descartes University
Patrick Bruneval: Paris Descartes University
Alexandre Loupy: Paris Descartes University
Sébastien Dussurgey: SFR Biosciences (UMS3444/CNRS, US8/Inserm, ENS de Lyon, UCBL)
Stéphanie Ducreux: Univ. Lyon
Vannary Meas-Yedid: Pasteur Institut
Jean-Christophe Olivo-Marin: Pasteur Institut
Héléna Paidassi: Univ. Lyon
Romain Guillemain: Cardiology and Heart Transplant Department
Jean-Luc Taupin: Saint-Louis Hospital
Jasper Callemeyn: University of Leuven
Emmanuel Morelon: Univ. Lyon
Antonino Nicoletti: Paris Diderot University
Béatrice Charreau: French National Institute of Health and Medical Research (Inserm) UMR1064
Valérie Dubois: Univ. Lyon
Maarten Naesens: University of Leuven
Thierry Walzer: Univ. Lyon
Thierry Defrance: Univ. Lyon
Olivier Thaunat: Univ. Lyon

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract Current doctrine is that microvascular inflammation (MVI) triggered by a transplant -recipient antibody response against alloantigens (antibody-mediated rejection) is the main cause of graft failure. Here, we show that histological lesions are not mediated by antibodies in approximately half the participants in a cohort of 129 renal recipients with MVI on graft biopsy. Genetic analysis of these patients shows a higher prevalence of mismatches between donor HLA I and recipient inhibitory killer cell immunoglobulin-like receptors (KIRs). Human in vitro models and transplantation of β2-microglobulin-deficient hearts into wild-type mice demonstrates that the inability of graft endothelial cells to provide HLA I-mediated inhibitory signals to recipient circulating NK cells triggers their activation, which in turn promotes endothelial damage. Missing self-induced NK cell activation is mTORC1-dependent and the mTOR inhibitor rapamycin can prevent the development of this type of chronic vascular rejection.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13113-5

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DOI: 10.1038/s41467-019-13113-5

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