Koenig, AliceAliceKoenigChen Chien ChiaMarçais, AntoineAntoineMarçaisBarba, ThomasThomasBarbaMathias, VirginieVirginieMathiasSicard, AntoineAntoineSicardRabeyrin, MaudMaudRabeyrinRacapé, MaudMaudRacapéDuong-Van-Huyen, Jean-PaulJean-PaulDuong-Van-HuyenBruneval, PatrickPatrickBrunevalLoupy, AlexandreAlexandreLoupyDussurgey, SébastienSébastienDussurgeyDucreux, StéphanieStéphanieDucreuxMeas-Yedid, VannaryVannaryMeas-YedidOlivo-Marin, Jean-ChristopheJean-ChristopheOlivo-MarinPaidassi, HélénaHélénaPaidassiGuillemain, RomainRomainGuillemainTaupin, Jean-LucJean-LucTaupinCallemeyn, JasperJasperCallemeynMorelon, EmmanuelEmmanuelMorelonNicoletti, AntoninoAntoninoNicolettiCharreau, BéatriceBéatriceCharreauDubois, ValérieValérieDuboisNaesens, MaartenMaartenNaesensWalzer, ThierryThierryWalzerDefrance, ThierryThierryDefranceThaunat, OlivierOlivierThaunat2020-09-292020-09-2920192041-1723https://scholars.lib.ntu.edu.tw/handle/123456789/515713Current 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.animationjournal article10.1038/s41467-019-13113-531767837WOS:000503001900001