Missing self triggers NK cell-mediated chronic vascular rejection of solid organ transplants - CIRI - Activation et transduction du signal dans les lymphocytes Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2019

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

Résumé

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.

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Immunologie
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hal-02387447 , version 1 (02-12-2019)

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Alice Koenig, Chien-Chia Chen, Antoine Marçais, Thomas Barba, Virginie Mathias, et al.. Missing self triggers NK cell-mediated chronic vascular rejection of solid organ transplants. Nature Communications, 2019, 10 (1), ⟨10.1038/s41467-019-13113-5⟩. ⟨hal-02387447⟩
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