https://scholars.lib.ntu.edu.tw/handle/123456789/515713
標題: | Missing self triggers NK cell-mediated chronic vascular rejection of solid organ transplants | 作者: | Koenig, Alice Chen Chien Chia Marçais, Antoine Barba, Thomas Mathias, Virginie Sicard, Antoine Rabeyrin, Maud Racapé, Maud Duong-Van-Huyen, Jean-Paul Bruneval, Patrick Loupy, Alexandre Dussurgey, Sébastien Ducreux, Stéphanie Meas-Yedid, Vannary Olivo-Marin, Jean-Christophe Paidassi, Héléna Guillemain, Romain Taupin, Jean-Luc Callemeyn, Jasper Morelon, Emmanuel Nicoletti, Antonino Charreau, Béatrice Dubois, Valérie Naesens, Maarten Walzer, Thierry Defrance, Thierry Thaunat, Olivier |
公開日期: | 2019 | 出版社: | NATURE PUBLISHING GROUP | 卷: | 10 | 期: | 1 | 來源出版物: | Nature communications | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/515713 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-019-13113-5 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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