Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation.
Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation.
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DOI：
10.1038/nature13801
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发表时间：
2015-01-01
期刊：
影响因子：
64.8
通讯作者：
Pellegrini, Sandra
中科院分区：
文献类型：
--
作者：
Zhang, Xianqin;Bogunovic, Dusan;Payelle-Brogard, Beatrice;Francois-Newton, Veronique;Speer, Scott D.;Yuan, Chao;Volpi, Stefano;Li, Zhi;Sanal, Ozden;Mansouri, Davood;Tezcan, Ilhan;Rice, Gillian I.;Chen, Chunyuan;Mansouri, Nahal;Mahdaviani, Seyed Alireza;Itan, Yuval;Boisson, Bertrand;Okada, Satoshi;Zeng, Lu;Wang, Xing;Jiang, Hui;Liu, Wenqiang;Han, Tiantian;Liu, Delin;Ma, Tao;Wang, Bo;Liu, Mugen;Liu, Jing-Yu;Wang, Qing K.;Yalnizoglu, Dilek;Radoshevich, Lilliana;Uze, Gilles;Gros, Philippe;Rozenberg, Flore;Zhang, Shen-Ying;Jouanguy, Emmanuelle;Bustamante, Jacinta;Garcia-Sastre, Adolfo;Abel, Laurent;Lebon, Pierre;Notarangelo, Luigi D.;Crow, Yanick J.;Boisson-Dupuis, Stephanie;Casanova, Jean-Laurent;Pellegrini, Sandra
细胞内ISG 15是一种干扰素（IFN）-α/β-诱导的泛素样修饰剂，可在称为ISGylation的过程中共价结合其他蛋白质;它是小鼠IFN-α/β依赖性抗病毒免疫的效应子。我们之前发表了一项研究，描述了患有遗传性ISG 15缺乏症但没有异常严重的病毒性疾病的人类。我们发现这些患者易于患分枝杆菌疾病，并且人ISG 15作为细胞外IFN-γ诱导分子是非冗余的。我们发现，ISG 15缺乏的患者也表现出IFN-α/β免疫增强的细胞、免疫学和临床症状，这让人想起孟德尔自身炎性干扰素病Aicardi-Goutières综合征和脊椎软骨发育不良。我们进一步表明，患者细胞内ISG 15的缺乏阻止了USP 18的积累，USP 18是IFN-α/β信号传导的有效负调节因子，导致IFN-α/β应答的增强和放大。因此，人ISG 15不仅对于抗病毒免疫是多余的，而且是IFN-α/β免疫的关键负调节剂。在人类中，细胞内ISG 15是IFN-α/β诱导型的，不作为I S G化依赖性抗病毒免疫的底物，但确保USP 18依赖性调节IFN-α/β和预防IFN-α/β依赖性自身炎症。
Intracellular ISG15 is an interferon (IFN)-α/β-inducible ubiquitin-like modifier which can covalently bind other proteins in a process called ISGylation; it is an effector of IFN-α/β-dependent antiviral immunity in mice. We previously published a study describing humans with inherited ISG15 deficiency but without unusually severe viral diseases. We showed that these patients were prone to mycobacterial disease and that human ISG15 was non-redundant as an extracellular IFN-γ-inducing molecule. We show here that ISG15-deficient patients also display unanticipated cellular, immunological and clinical signs of enhanced IFN-α/β immunity, reminiscent of the Mendelian autoinflammatory interferonopathies Aicardi–Goutières syndrome and spondyloenchondrodysplasia.We further show that an absence of intracellular ISG15 in the patients’ cells prevents the accumulation of USP18, a potent negative regulator of IFN-α/β signalling, resulting in the enhancement and amplification of IFN-α/β responses. Human ISG15, therefore, is not only redundant for antiviral immunity, but is a key negative regulator of IFN-α/β immunity. In humans, intracellular ISG15 is IFN-α/β-inducible not to serve as a substrate for ISGylation-dependent antiviral immunity, but to ensure USP18-dependent regulation of IFN-α/β and prevention of IFN-α/β-dependent autoinflammation.
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影响因子：
64.5
作者：
Skaug B;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
30.8
作者：
Keller, Annika;Westenberger, Ana;Oliveira, Joao R. M.
通讯作者：
Oliveira, Joao R. M.
影响因子：
30.8
作者：
Briggs, Tracy A.;Rice, Gillian I.;Daly, Sarah;Urquhart, Jill;Gornall, Hannah;Bader-Meunier, Brigitte;Baskar, Kannan;Baskar, Shankar;Baudouin, Veronique;Beresford, Michael W.;Black, Graeme C. M.;Dearman, Rebecca J.;de Zegher, Francis;Foster, Emily S.;Frances, Camille;Hayman, Alison R.;Hilton, Emma;Job-Deslandre, Chantal;Kulkarni, Muralidhar L.;Le Merrer, Martine;Linglart, Agnes;Lovell, Simon C.;Maurer, Kathrin;Musset, Lucile;Navarro, Vincent;Picard, Capucine;Puel, Anne;Rieux-Laucat, Frederic;Roifman, Chaim M.;Scholl-Buergi, Sabine;Smith, Nigel;Szynkiewicz, Marcin;Wiedeman, Alice;Wouters, Carine;Zeef, Leo A. H.;Casanova, Jean-Laurent;Elkon, Keith B.;Janckila, Anthony;Lebon, Pierre;Crow, Yanick J.
通讯作者：
Crow, Yanick J.
影响因子：
4.1
作者：
Francois-Newton, Veronique;Livingstone, Mark;Pellegrini, Sandra
通讯作者：
Pellegrini, Sandra
DOI：
10.1126/science.1224026
发表时间：
2012-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bogunovic D;Byun M;Durfee LA;Abhyankar A;Sanal O;Mansouri D;Salem S;Radovanovic I;Grant AV;Adimi P;Mansouri N;Okada S;Bryant VL;Kong XF;Kreins A;Velez MM;Boisson B;Khalilzadeh S;Ozcelik U;Darazam IA;Schoggins JW;Rice CM;Al-Muhsen S;Behr M;Vogt G;Puel A;Bustamante J;Gros P;Huibregtse JM;Abel L;Boisson-Dupuis S;Casanova JL
通讯作者：
Casanova JL