dc.contributor.author | Zhang, Xianqin | |
dc.contributor.author | Bogunovic, Dusan | |
dc.contributor.author | Payelle-Brogard, Beatrice | |
dc.contributor.author | Francois-Newton, Veronique | |
dc.contributor.author | Speer, Scott D. | |
dc.contributor.author | Yuan, Chao | |
dc.contributor.author | Volpi, Stefano | |
dc.contributor.author | Li, Zhi | |
dc.contributor.author | Sanal, Ozden | |
dc.contributor.author | Mansouri, Davood | |
dc.contributor.author | Tezcan, Ilhan | |
dc.contributor.author | Rice, Gillian I. | |
dc.contributor.author | Chen, Chunyuan | |
dc.contributor.author | Mansouri, Nahal | |
dc.contributor.author | Mahdaviani, Seyed Alireza | |
dc.contributor.author | Itan, Yuval | |
dc.contributor.author | Boisson, Bertrand | |
dc.contributor.author | Okada, Satoshi | |
dc.contributor.author | Zeng, Lu | |
dc.contributor.author | Wang, Xing | |
dc.contributor.author | Jiang, Hui | |
dc.contributor.author | Liu, Wenqiang | |
dc.contributor.author | Han, Tiantian | |
dc.contributor.author | Liu, Delin | |
dc.contributor.author | Ma, Tao | |
dc.contributor.author | Wang, Bo | |
dc.contributor.author | Liu, Mugen | |
dc.contributor.author | Liu, Jing-Yu | |
dc.contributor.author | Wang, Qing K. | |
dc.contributor.author | Yalnizoglu, Dilek | |
dc.contributor.author | Radoshevich, Lilliana | |
dc.contributor.author | Uze, Gilles | |
dc.contributor.author | Gros, Philippe | |
dc.contributor.author | Rozenberg, Flore | |
dc.contributor.author | Zhang, Shen-Ying | |
dc.contributor.author | Jouanguy, Emmanuelle | |
dc.contributor.author | Bustamante, Jacinta | |
dc.contributor.author | Garcia-Sastre, Adolfo | |
dc.contributor.author | Abel, Laurent | |
dc.contributor.author | Lebon, Pierre | |
dc.contributor.author | Notarangelo, Luigi D. | |
dc.contributor.author | Crow, Yanick J. | |
dc.contributor.author | Boisson-Dupuis, Stephanie | |
dc.contributor.author | Casanova, Jean-Laurent | |
dc.contributor.author | Pellegrini, Sandra | |
dc.date.accessioned | 2019-12-10T10:52:16Z | |
dc.date.available | 2019-12-10T10:52:16Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 0028-0836 | |
dc.identifier.uri | https://doi.org/10.1038/nature13801 | |
dc.identifier.uri | http://hdl.handle.net/11655/14526 | |
dc.description.abstract | Intracellular ISG15 is an interferon (IFN)-alpha/beta-inducible ubiquitin-like modifier which can covalently bind other proteins in a process called ISGylation; it is an effector of IFN-alpha/beta-dependent antiviral immunity in mice(1-4). We previously published a study describing humans with inherited ISG15deficiency but without unusually severe viral diseases(5). We showed that these patients were prone to mycobacterial disease and that human ISG15 was non-redundant as an extracellular IFN-gamma-inducing molecule. We show here that ISG15-deficient patients also display unanticipated cellular, immunological and clinical signs of enhanced IFN-alpha/beta immunity, reminiscent of the Mendelian autoinflammatory interferonopathies Aicardi-Goutieres syndrome and spondyloenchondrodysplasia(6-9). We further show that an absence of intracellular ISG15 in the patients' cells prevents the accumulation of USP18(10,11), a potent negative regulator of IFN-alpha/beta signalling, resulting in the enhancement and amplification of IFN-alpha/beta responses. Human ISG15, therefore, is not only redundant for antiviral immunity, but is a key negative regulator of IFN-alpha/beta immunity. In humans, intracellular ISG15 is IFN-alpha/beta-inducible not to serve as a substrate for ISGylation-dependent antiviral immunity, but to ensure USP18-dependent regulation of IFN-alpha/beta and prevention of IFN-alpha/beta-dependent autoinflammation. | |
dc.language.iso | en | |
dc.publisher | Nature Publishing Group | |
dc.relation.isversionof | 10.1038/nature13801 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | Science & Technology - Other Topics | |
dc.title | Human Intracellular Isg15 Prevents Interferon-Alpha/Beta Over-Amplification And Auto-Inflammation | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:eu-repo/semantics/publishedVersion | |
dc.relation.journal | Nature | |
dc.contributor.department | Çocuk ve Ergen Ruh Sağlığı ve Hastalıkları | |
dc.identifier.volume | 517 | |
dc.identifier.issue | 7532 | |
dc.identifier.startpage | 89 | |
dc.identifier.endpage | U229 | |
dc.description.index | WoS | |