| Title |
Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation
|
|---|---|
| Published in |
Nature, October 2014
|
| DOI | 10.1038/nature13801 |
| Pubmed ID | |
| Authors |
Xianqin Zhang, Dusan Bogunovic, Béatrice Payelle-Brogard, Véronique Francois-Newton, Scott D. Speer, Chao Yuan, Stefano Volpi, Zhi Li, Ozden Sanal, Davood Mansouri, Ilhan Tezcan, Gillian I. Rice, Chunyuan Chen, Nahal Mansouri, Seyed Alireza Mahdaviani, Yuval Itan, Bertrand Boisson, Satoshi Okada, Lu Zeng, Xing Wang, Hui Jiang, Wenqiang Liu, Tiantian Han, Delin Liu, Tao Ma, Bo Wang, Mugen Liu, Jing-Yu Liu, Qing K. Wang, Dilek Yalnizoglu, Lilliana Radoshevich, Gilles Uzé, Philippe Gros, Flore Rozenberg, Shen-Ying Zhang, Emmanuelle Jouanguy, Jacinta Bustamante, Adolfo García-Sastre, Laurent Abel, Pierre Lebon, Luigi D. Notarangelo, Yanick J. Crow, Stéphanie Boisson-Dupuis, Jean-Laurent Casanova, Sandra Pellegrini |
| Abstract |
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. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 40% |
| Unknown | 3 | 60% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 60% |
| Scientists | 2 | 40% |
Mendeley readers
The data shown below were compiled from readership statistics for 460 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 5 | 1% |
| United Kingdom | 3 | <1% |
| Brazil | 1 | <1% |
| France | 1 | <1% |
| Spain | 1 | <1% |
| Austria | 1 | <1% |
| Unknown | 448 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 109 | 24% |
| Researcher | 82 | 18% |
| Student > Master | 48 | 10% |
| Student > Bachelor | 38 | 8% |
| Professor > Associate Professor | 25 | 5% |
| Other | 79 | 17% |
| Unknown | 79 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 116 | 25% |
| Biochemistry, Genetics and Molecular Biology | 92 | 20% |
| Immunology and Microbiology | 78 | 17% |
| Medicine and Dentistry | 50 | 11% |
| Neuroscience | 8 | 2% |
| Other | 25 | 5% |
| Unknown | 91 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 36. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 December 2022.
All research outputs
#1,165,528
of 26,052,823 outputs
Outputs from Nature
#34,427
of 99,406 outputs
Outputs of similar age
#12,442
of 270,466 outputs
Outputs of similar age from Nature
#570
of 1,082 outputs
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