Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ISG15, an interferon-inducible protein necessary for viral protection in mice, does not have the same critical role in humans.
“Similarly, ISG15, an interferon-inducible protein necessary for viral protection in mice, does not have the same critical role in humans(48-50).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [49]
Soluble TRAIL activates cell death pathways in hepatocytes in response to ethanol consumption and has been implicated in hepatic steatosis and hepatocyte death in ASH.
“Soluble TRAIL activates cell death pathways in hepatocytes in response to ethanol consumption and has been implicated in hepatic steatosis and hepatocyte death in ASH (49).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [49]
The Methods (Cell lines and reagents) and Extended Data passages concern interferon responses and ISG15-deficient cells, not liver injury. Searches for soluble TRAIL, ethanol, hepatocytes, steatosis, and alcoholic steatohepatitis found no passage in our copy addressing the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Baechler, E. C., Batliwalla, F., Karypis, G., Gaffney, P. M., Ortmann, W. A., Espe, K. J., Shark, K. B., Grande, W. J., Hughes, K. M. H., Kapur, V., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0337679100 · Cited by 2,246 · see citing works
Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood
Bennett, L. B., Palucka, K., Arce, E., Cantrell, V., Borvák, J., Banchereau, J., & Pascual, V. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021553 · Cited by 1,962 · see citing works
Genetic Dissection of Immunity to Mycobacteria: The Human Model
Casanova, J., & Abel, L. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.081501.125851 · Cited by 987 · see citing works
Self-citationDeregulated proteolysis by the F-box proteins SKP2 and β-TrCP: tipping the scales of cancer
Frescas, D., & Pagano, M. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2396 · Cited by 886 · see citing works
Mycobacterial Disease and Impaired IFN-γ Immunity in Humans with Inherited ISG15 Deficiency
Bogunovic, D., Byun, M., Durfee, L. A., Abhyankar, A., Sanal, O., Mansouri, D., Salem, S., Radovanovic, I., Grant, A. V., Adimi, P., et al. (2012) · Science · doi:10.1126/science.1224026 · Cited by 572 · see citing works
Self-citationRice, G., Forte, G. M. A., Szynkiewicz, M., Chase, D. S., Aeby, A., Abdel‐Hamid, M. S., Ackroyd, S., Allcock, R., Bailey, K. M., Balottin, U., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70258-8 · Cited by 444 · see citing works
Self-citationUBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity
Malakhova, O. A., Kim, K. I. I., Luo, J.-K., Zou, W., Kumar, K. G., Fuchs, S. Y., Shuai, K., & Zhang, D. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601149 · Cited by 430 · see citing works
Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis
Wang, C., Li, Y., Shi, L., Ren, J., Patti, M., Wang, T., de Oliveira, J. R. M., Sobrido, M. J., Quintáns, B., Baquero, M., et al. (2012) · Nature Genetics · doi:10.1038/ng.1077 · Cited by 417 · see citing works
Self-citationWhat is and what is not ‘Fahr's disease’
Manyam, B. V. (2005) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2004.12.001 · Cited by 395 · see citing works
Durfee, L. A., Lyon, N., Seo, K., & Huibregtse, J. M. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.002 · Cited by 359 · see citing works
Interferon-Stimulated Gene 15 and the Protein ISGylation System
Zhang, D., & Zhang, D. (2010) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2010.0110 · Cited by 351 · see citing works
Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice
Keller, A., Westenberger, A., Sobrido, M. J., García-Murias, M., Domingo, A., Sears, R. L., Lemos, R. R., Ordoñez-Ugalde, A., Nicolas, G., da Cunha, J. E. G., et al. (2013) · Nature Genetics · doi:10.1038/ng.2723 · Cited by 324 · see citing works
Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity
Crow, Y. J., & Rehwinkel, J. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp293 · Cited by 289 · see citing works
Self-citationMutation of the <i>PDGFRB</i> gene as a cause of idiopathic basal ganglia calcification
Nicolas, G., Pottier, C., Maltête, D., Coutant, S., Rovelet-Lecrux, A., Legallic, S., Rousseau, S., Vaschalde, Y., Guyant-Maréchal, L., Augustin, J., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e31827ccf34 · Cited by 279 · see citing works
François-Newton, V., Almeida, G. M. D. F., Payelle‐Brogard, B., Monneron, D., Pichard‐Garcia, L., Piehler, J., Pellegrini, S., & Uzé, G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022200 · Cited by 270 · see citing works
Self-citationBriggs, T. A., Rice, G., Daly, S. B., Urquhart, J. E., Gornall, H., Bader‐Meunier, B., Baskar, K., Baskar, S., Baudouin, V., Beresford, M. W., et al. (2011) · Nature Genetics · doi:10.1038/ng.748 · Cited by 261 · see citing works
Self-citationThe Antiviral Activities of ISG15
Morales, D. J., & Lenschow, D. J. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.09.041 · Cited by 256 · see citing works
Emerging Role of ISG15 in Antiviral Immunity
Skaug, B. A., & Chen, Z. J. (2010) · Cell · doi:10.1016/j.cell.2010.09.033 · Cited by 222 · see citing works
Li, Q. Z., Zhou, J., Wandstrat, A. E., Carr-Johnson, F., Branch, V. K., Karp, D. R., Mohan, C., Wakeland, E. K., & Olsen, N. J. (2006) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2006.03251.x · Cited by 189 · see citing works
The Genetic Theory of Infectious Diseases: A Brief History and Selected Illustrations
Casanova, J., & Abel, L. (2013) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091212-153448 · Cited by 176 · see citing works
Self-citationJeon, Y. J., Yoo, H. M., & Chung, C. H. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.02.006 · Cited by 171 · see citing works
ISG15: leading a double life as a secreted molecule
Bogunovic, D., Boisson‐Dupuis, S., & Casanova, J. (2013) · Experimental & Molecular Medicine · doi:10.1038/emm.2013.36 · Cited by 124 · see citing works
Self-citationFine tuning type I interferon responses
Hertzog, P. J., & Williams, B. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.04.002 · Cited by 122 · see citing works
Crow, Y. J. (2013) · Handbook of clinical neurology · doi:10.1016/b978-0-444-59565-2.00031-9 · Cited by 115 · see citing works
Self-citationBroering, R., Zhang, X., Kottilil, S., Trippler, M., Jiang, M., Lu, M., Gerken, G., & Schlaak, J. (2010) · Gut · doi:10.1136/gut.2009.195545 · Cited by 96 · see citing works
Self-citationBrain calcification in patients with cerebral lupus
Raymond, A. A., Zariah, A., Samad, S., Chin, C., & Kong, N. (1996) · Lupus · doi:10.1177/096120339600500207 · Cited by 87 · see citing works
Recognizable phenotypes associated with intracranial calcification
Livingston, J. H., Stivaros, S. M., van der Knaap, M. S., & Crow, Y. J. (2012) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2012.04437.x · Cited by 78 · see citing works
Self-citationIntracranial calcification in paediatric computed tomography
Kendall, B. E., & Cavanagh, N. P. (1986) · Neuroradiology · doi:10.1007/bf00333438 · Cited by 61 · see citing works
The ISG15 Isopeptidase UBP43 Is Regulated by Proteolysis via the SCFSkp2 Ubiquitin Ligase
Tokarz, S. A., Berset, C., LaRUE, J. M., Friedman, K. M., Nakayama, K., Nakayama, K., Zhang, D., & Lanker, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403189200 · Cited by 58 · see citing works
USP18 establishes the transcriptional and anti-proliferative interferon α/β differential
François-Newton, V., Livingstone, M., Payelle‐Brogard, B., Uzé, G., & Pellegrini, S. (2012) · Biochemical Journal · doi:10.1042/bj20120541 · Cited by 54 · see citing works
Self-citationModulation of alpha interferon anti-hepatitis C virus activity by ISG15
Chua, P. K., McCown, M. F., Rajyaguru, S., Kular, S., Varma, R., Symons, J. A., Chiu, S. S., Cammack, N., & Nájera, I. (2009) · Journal of General Virology · doi:10.1099/vir.0.013128-0 · Cited by 44 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [1]Jeon YJ Yoo HM Chung CH ISG15and immune diseases Biochim. Biophys. Acta 2010 1802 485 496 20153823 PMC7127291
Cited by
Sorted by citations
New insights into the immunopathogenesis of systemic lupus erythematosus
Tsokos, G. C., Lo, M. S., Costa‐Reis, P., & Sullivan, K. E. (2016) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2016.186 · Cited by 1,225 · see citing works
Shared and Distinct Functions of Type I and Type III Interferons
Lazear, H. M., Schoggins, J. W., & Diamond, M. S. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.025 · Cited by 1,138 · see citing works
Aicardi–Goutières syndrome and the type I interferonopathies
Crow, Y. J., & Manel, N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3850 · Cited by 925 · see citing works
Self-citationISG15 in antiviral immunity and beyond
Perng, Y.-C., & Lenschow, D. J. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0020-5 · Cited by 855 · see citing works
The JAK-STAT pathway at 30: Much learned, much more to do
Philips, R. L., Wang, Y., Cheon, H., Kanno, Y., Gadina, M., Sartorelli, V., Horvath, C. M., Darnell, J. E., Jr., Stark, G. R., & O’Shea, J. J. (2022) · Cell · doi:10.1016/j.cell.2022.09.023 · Cited by 740 · see citing works
Ubiquitin-Dependent And Independent Signals In Selective Autophagy
Khaminets, A., Behl, C., & Đikić, I. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.08.010 · Cited by 716 · see citing works
Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease
Roy, E. R., Wang, B., Wan, Y.-W., Chiu, G., Cole, A., Yin, Z., Propson, N. E., Xu, Y., Jankowsky, J. L., Liu, Z., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133737 · Cited by 563 · see citing works
Self-citationUbiquitin-like Protein Conjugation: Structures, Chemistry, and Mechanism
Cappadocia, L., & Lima, C. D. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00737 · Cited by 548 · see citing works
ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins
Villarroya‐Beltri, C., Baixauli, F., Mittelbrunn, M., Fernández‐Delgado, I., Torralba, D., Moreno-Gonzalo, O., Baldanta, S., Enrich, C., Guerra, S., & Sánchez‐Madrid, F. (2016) · Nature Communications · doi:10.1038/ncomms13588 · Cited by 489 · see citing works
The type I interferonopathies: 10 years on
Crow, Y. J., & Stetson, D. B. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-021-00633-9 · Cited by 489 · see citing works
Self-citationRodero, M. P., & Crow, Y. J. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20161596 · Cited by 433 · see citing works
Self-citationImmune responses and immunopathology in acute and chronic viral hepatitis
Shin, E., Sung, P. S., & Park, S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.69 · Cited by 362 · see citing works
Liu, G., Lee, J., Parker, Z. M., Acharya, D., Chiang, J. J., van Gent, M., Riedl, W., Davis-Gardner, M. E., Wies, E., Chiang, C., et al. (2021) · Nature Microbiology · doi:10.1038/s41564-021-00884-1 · Cited by 344 · see citing works
Majoros, A., Platanitis, E., Kernbauer, E., Rosebrock, F., Müller, M. M., & Decker, T. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00029 · Cited by 321 · see citing works
Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome
Meuwissen, M. E. C., Schot, R., Buta, S., Oudesluijs, G., Tinschert, S., Speer, S. D., Li, Z., van Unen, L., Heijsman, D., Goldmann, T., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20151529 · Cited by 289 · see citing works
Self-citationType I interferons in tuberculosis: Foe and occasionally friend
Moreira-Teixeira, L., Mayer-Barber, K. D., Sher, A., & O’Garra, A. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180325 · Cited by 273 · see citing works
Scanu, T., Spaapen, R. M., Bakker, J. M., Pratap, C. B., Wu, L.-E., Hofland, I., Broeks, A., Shukla, V. K., Mohan Kumar, H., Janssen, H., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.05.002 · Cited by 269 · see citing works
Host-directed immunotherapy of viral and bacterial infections: past, present and future
Wallis, R. S., O’Garra, A., Sher, A., & Wack, A. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00734-z · Cited by 268 · see citing works
Forero, A., Ozarkar, S., Li, H., Lee, C. H., Hemann, E. A., Nadjsombati, M. S., Hendricks, M. R., So, L., Green, R. R., Roy, C. N., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.07.007 · Cited by 267 · see citing works
Extracellular ISG15 Signals Cytokine Secretion through the LFA-1 Integrin Receptor
Swaim, C. D., Scott, A. F., Canadeo, L. A., & Huibregtse, J. M. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.10.003 · Cited by 238 · see citing works
Inherited and acquired immunodeficiencies underlying tuberculosis in childhood
Boisson‐Dupuis, S., Bustamante, J. C., Baghdadi, J. E., Çamcıoğlu, Y., Parvaneh, N., Azbaoui, S. E., Agader, A., Hassani, A., Hafidi, N. E., Mrani, N. A., et al. (2015) · Immunological Reviews · doi:10.1111/imr.12272 · Cited by 224 · see citing works
Self-citationUSP18 lack in microglia causes destructive interferonopathy of the mouse brain
Goldmann, T., Zeller, N., Raasch, J., Kierdorf, K., Frenzel, K., Ketscher, L., Basters, A., Staszewski, O., Brendecke, S. M., Spiess, A., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490791 · Cited by 223 · see citing works
Transcriptional Regulation of Antiviral Interferon-Stimulated Genes
Wang, W., Xu, L., Su, J., Peppelenbosch, M. P., & Pan, Q. (2017) · Trends in Microbiology · doi:10.1016/j.tim.2017.01.001 · Cited by 221 · see citing works
Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling
Lepelley, A., Martin-Niclós, M. J., Bihan, M. L., Marsh, J. A., Uggenti, C., Rice, G., Bondet, V., Duffy, D., Hertzog, J., Rehwinkel, J., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20200600 · Cited by 221 · see citing works
Self-citationIntracellular Nucleic Acid Detection in Autoimmunity
Crowl, J. T., Gray, E. E., Pestal, K., Volkman, H. E., & Stetson, D. B. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052331 · Cited by 217 · see citing works
Exome and genome sequencing for inborn errors of immunity
Meyts, I., Bosch, B., Bolze, A., Boisson, B., Itan, Y., Belkadi, A., Pedergnana, V., Moens, L., Pïcard, C., Cobat, A., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.08.003 · Cited by 215 · see citing works
Self-citationOverview of STING-Associated Vasculopathy with Onset in Infancy (SAVI) Among 21 Patients
Frémond, M., Hadchouel, A., Berteloot, L., Melki, I., Bresson, V., Barnabei, L., Jeremiah, N., Bélot, A., Bondet, V., Brocq, O., et al. (2020) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2020.11.007 · Cited by 215 · see citing works
Self-citationThe Ubiquitin–Proteasome System in Immune Cells
Çetin, G., Klafack, S., Studencka‐Turski, M., Krüger, E., & Ebstein, F. (2021) · Biomolecules · doi:10.3390/biom11010060 · Cited by 210 · see citing works
Remick, B. C., Gaidt, M. M., & Vance, R. E. (2023) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101721-031732 · Cited by 209 · see citing works
Lee‐Kirsch, M. A. (2016) · Annual Review of Medicine · doi:10.1146/annurev-med-050715-104506 · Cited by 208 · see citing works
STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling
Arimoto, K., Löchte, S., Stoner, S. A., Burkart, C., Zhang, Y., Miyauchi, S., Wilmes, S., Fan, J.-B., Heinisch, J. J., Li, Z., et al. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3378 · Cited by 205 · see citing works
Self-citationAssessment of Type I Interferon Signaling in Pediatric Inflammatory Disease
Rice, G., Melki, I., Frémond, M., Briggs, T. A., Rodero, M. P., Kitabayashi, N., Oojageer, A., Bader‐Meunier, B., Bélot, A., Bodemer, C., et al. (2016) · Journal of Clinical Immunology · doi:10.1007/s10875-016-0359-1 · Cited by 203 · see citing works
Self-citationISG15 deficiency and increased viral resistance in humans but not mice
Speer, S. D., Li, Z., Buta, S., Payelle‐Brogard, B., Li, Q., Vigant, F., Rubino, E., Gardner, T. J., Wedeking, T., Hermann, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms11496 · Cited by 202 · see citing works
Self-citationDynamic control of type I IFN signalling by an integrated network of negative regulators
Porritt, R. A., & Hertzog, P. J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.002 · Cited by 198 · see citing works
Honke, N., Shaabani, N., Zhang, D., Hardt, C., & Lang, K. S. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.326 · Cited by 180 · see citing works
Hepatitis C Virus Infection: Host–Virus Interaction and Mechanisms of Viral Persistence
Chigbu, D. I., Loonawat, R., Sehgal, M., Patel, D., & Jain, P. (2019) · Cells · doi:10.3390/cells8040376 · Cited by 178 · see citing works
LRRC25 inhibits type I IFN signaling by targeting ISG15‐associated RIG‐I for autophagic degradation
Du, Y., Duan, T., Feng, Y., Liu, Q., Lin, M., Cui, J., & Wang, R. (2017) · The EMBO Journal · doi:10.15252/embj.201796781 · Cited by 170 · see citing works
ISGylation – a key to lock the cell gates for preventing the spread of threats
Villarroya‐Beltri, C., Guerra, S., & Sánchez‐Madrid, F. (2017) · Journal of Cell Science · doi:10.1242/jcs.205468 · Cited by 167 · see citing works
Type I interferon pathway in CNS homeostasis and neurological disorders
Blank, T., & Prinz, M. (2017) · Glia · doi:10.1002/glia.23154 · Cited by 165 · see citing works
Monogenic Lupus: A Developing Paradigm of Disease
Alperin, J. M., Ortiz‐Fernández, L., & Sawalha, A. H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02496 · Cited by 163 · see citing works
No Love Lost Between Viruses and Interferons
Fensterl, V., Chattopadhyay, S., & Sen, G. C. (2015) · Annual Review of Virology · doi:10.1146/annurev-virology-100114-055249 · Cited by 162 · see citing works
Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification
Yao, X., Cheng, X., Wang, C., Zhao, M., Guo, X.-X., Su, H., Lai, L., Zou, X.-H., Chen, X., Zhao, Y., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.05.037 · Cited by 160 · see citing works
Dzimianski, J. V., Scholte, F. E. M., Bergeron, É., & Pegan, S. D. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.03.013 · Cited by 159 · see citing works
Monogenic autoinflammatory disorders: Conceptual overview, phenotype, and clinical approach
Nigrovic, P. A., Lee, P. Y., & Hoffman, H. M. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.08.017 · Cited by 158 · see citing works
Human TBK1 deficiency leads to autoinflammation driven by TNF-induced cell death
Taft, J., Markson, M., Legarda, D., Patel, R., Chan, M., Malle, L., Richardson, A., Gruber, C., Martín-Fernández, M., Mancini, G. M. S., et al. (2021) · Cell · doi:10.1016/j.cell.2021.07.026 · Cited by 151 · see citing works
Self-citationTRIM25 in the Regulation of the Antiviral Innate Immunity
Martin‐Vicente, M., Medrano, L. M., Resino, S., García‐Sastre, A., & Martínez, I. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01187 · Cited by 148 · see citing works
Self-citationDemirkaya, E., Şahin, S., Romano, M., Zhou, Q., & Aksentijevich, I. A. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9030712 · Cited by 148 · see citing works
DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis
Starokadomskyy, P., Gemelli, T., Rios, J. J., Xing, C., Wang, R. C., Li, H., Pokatayev, V., Dozmorov, I. M., Khan, S., Miyata, N., et al. (2016) · Nature Immunology · doi:10.1038/ni.3409 · Cited by 146 · see citing works
Translating nucleic acid-sensing pathways into therapies
Junt, T., & Barchet, W. (2015) · Nature reviews. Immunology · doi:10.1038/nri3875 · Cited by 145 · see citing works
Inherited human IFN-γ deficiency underlies mycobacterial disease
Kerner, G., Rosain, J., Guérin, A., Al-Khabaz, A., Oleaga‐Quintas, C., Rapaport, F., Massaad, M. J., Ding, J.-Y., Khan, T., Ali, F. A., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci135460 · Cited by 141 · see citing works
Self-citationSelf-Awareness: Nucleic Acid–Driven Inflammation and the Type I Interferonopathies
Uggenti, C., Lepelley, A., & Crow, Y. J. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041257 · Cited by 138 · see citing works
Self-citationHuman T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria
Yang, R., Mele, F., Worley, L., Langlais, D., Rosain, J., Benhsaien, I., Elarabi, H., Croft, C. A., Doisne, J., Zhang, P., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.046 · Cited by 138 · see citing works
Self-citationAltered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection
Munnur, D., Teo, Q. W., Eggermont, D., Lee, H. H. Y., Théry, F., Ho, J., van Leur, S. W., Ng, W. W., Siu, L. Y.-L., Beling, A., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-01035-8 · Cited by 137 · see citing works
Long noncoding RNAs in viral infections
Fortes, P., & Morris, K. V. (2015) · Virus Research · doi:10.1016/j.virusres.2015.10.002 · Cited by 134 · see citing works
Békés, M., van Noort, G. J. V. D. H., Ekkebus, R., Ovaa, H., Huang, T. T., & Lima, C. D. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.04.016 · Cited by 134 · see citing works
Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity
Théry, F., Martina, L., Asselman, C., Zhang, Y., Vessely, M., Repo, H., Sedeyn, K., Moschonas, G. D., Bredow, C., Teo, Q. W., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26061-w · Cited by 133 · see citing works
Self-citationType I interferonopathies in pediatric rheumatology
Volpi, S., Picco, P. P., Caorsi, R., Candotti, F., & Gattorno, M. (2016) · Pediatric Rheumatology · doi:10.1186/s12969-016-0094-4 · Cited by 130 · see citing works
Self-citationStructural basis of the specificity of USP18 toward ISG15
Basters, A., Geurink, P. P., Röcker, A., Witting, K. F., Tadayon, R., Hess, S., Semrau, M. S., Storici, P., Ovaa, H., Knobeloch, K., et al. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3371 · Cited by 130 · see citing works
Disorders of ubiquitylation: unchained inflammation
Beck, D. B., Werner, A. A., Kastner, D. L., & Aksentijevich, I. A. (2022) · Nature Reviews Rheumatology · doi:10.1038/s41584-022-00778-4 · Cited by 130 · see citing works
ISG15 counteracts Listeria monocytogenes infection
Radoshevich, L., Impens, F., Ribet, D., Quereda, J. J., Tham, T. N., Nahori, M., Bierne, H., Dussurget, O., Pizarro‐Cerdá, J., Knobeloch, K., et al. (2015) · eLife · doi:10.7554/elife.06848 · Cited by 129 · see citing works
Self-citationSinghania, A., Wilkinson, R. J., Rodrigue, M., Haldar, P., & O’Garra, A. (2018) · Nature Immunology · doi:10.1038/s41590-018-0225-9 · Cited by 124 · see citing works
Salem, S., Salem, D., & Gros, P. (2020) · Human Genetics · doi:10.1007/s00439-020-02154-2 · Cited by 124 · see citing works
Self-citationMladinich, M. C., Schwedes, J. F., & Mackow, E. R. (2017) · mBio · doi:10.1128/mbio.00952-17 · Cited by 123 · see citing works
Gruber, C. N., Martín-Fernández, M., Ailal, F., Qiu, X., Taft, J. D., Altman, J. B., Rosain, J., Buta, S., Bousfiha, A. A., Casanova, J., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20192319 · Cited by 123 · see citing works
Self-citationStanding on the shoulders of mice
Medetgul-Ernar, K., & Davis, M. M. (2022) · Immunity · doi:10.1016/j.immuni.2022.07.008 · Cited by 119 · see citing works
Negative regulation of type I IFN signaling
Arimoto, K.-I., Miyauchi, S., Stoner, S. A., Fan, J.-B., & Zhang, D.-E. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.2mir0817-342r · Cited by 117 · see citing works
Genome-wide CRISPR screen for Zika virus resistance in human neural cells
Li, Y., Muffat, J., Omer, A., Keys, H. R., Lungjangwa, T., Bosch, I., Khan, M., Virgilio, M., Gehrke, L., Sabatini, D. M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900867116 · Cited by 116 · see citing works
Duncan, C. J. A., Thompson, B. J., Chen, R., Rice, G., Gothe, F., Young, D. F., Lovell, S. C., Shuttleworth, V. G., Brocklebank, V., Corner, B. M., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aav7501 · Cited by 115 · see citing works
Self-citationISG15: In Sickness and in Health
Hermann, M., & Bogunovic, D. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.11.001 · Cited by 113 · see citing works
Self-citationLiu, W., Liao, X., Luo, Z., Yang, Y., Lau, M. C., Jiao, Y., Shi, X., Zhai, W., Ji, H., Yeong, J. P.-S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-35947-w · Cited by 113 · see citing works
Self-citationHost genetics of severe influenza: from mouse Mx1 to human IRF7
Ciancanelli, M. J., Abel, L., Zhang, S., & Casanova, J. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2015.12.002 · Cited by 111 · see citing works
Self-citationResponses to Cytokines and Interferons that Depend upon JAKs and STATsPreprint
Stark, G. R., Cheon, H., & Wang, Y. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028555 · Cited by 111 · see citing works
Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey
Briggs, T. A., Rice, G., Adib, N., Adès, L. C., Barète, S., Baskar, K., Baudouin, V., Cebeci, A. N., Clapuyt, P. R. M., Coman, D. J., et al. (2016) · Journal of Clinical Immunology · doi:10.1007/s10875-016-0252-y · Cited by 110 · see citing works
Self-citationPositive feedback regulation of p53 transactivity by DNA damage-induced ISG15 modification
Park, J., Yang, S. W., Park, J. M., Ka, S. H., Kim, J.-H., Kong, Y., Jeon, Y. J., Seol, J. H., & Chung, C. H. (2016) · Nature Communications · doi:10.1038/ncomms12513 · Cited by 110 · see citing works
Zhao, C., Sridharan, H., Chen, R., Baker, D. P., Wang, S., & Krug, R. M. (2016) · Nature Communications · doi:10.1038/ncomms12754 · Cited by 110 · see citing works
Zhang, Y., Guo, X., Yan, W., Chen, Y., Ke, M., Cheng, C., Zhu, X., Xue, W., Zhou, Q., Zheng, L., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02355-w · Cited by 107 · see citing works
Zhang, Y., Théry, F., Wu, N. C., Luhmann, E. K., Dussurget, O., Foecke, M. H., Bredow, C., Jiménez-Fernández, D., Leandro, K., Beling, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13393-x · Cited by 107 · see citing works
Self-citationISG15 governs mitochondrial function in macrophages following vaccinia virus infection
Baldanta, S., Fernández‐Escobar, M., Acín‐Pérez, R., Albert, M., Camafeita, E., Jorge, I., Vázquez, J., Enrı́quez, J. A., & Guerra, S. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006651 · Cited by 105 · see citing works
JAK Inhibitor Therapy in a Child with Inherited USP18 Deficiency
Alsohime, F., Martín-Fernández, M., Temsah, M.-H. A., Alabdulhafid, M., Voyer, T. L., Alghamdi, M. A., Qiu, X., Alotaibi, N., Alkahtani, A. R., Buta, S., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1905633 · Cited by 105 · see citing works
Self-citationThe diverse repertoire of ISG15: more intricate than initially thought
Kang, J. A., Kim, Y. J., & Jeon, Y. J. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00872-3 · Cited by 105 · see citing works
An, S., Zhao, L., She, Z., Wang, S., Zhang, K., Yu, Q., Zheng, J., Zhang, X., Zhu, X., Bao, R., et al. (2017) · Hepatology · doi:10.1002/hep.29375 · Cited by 104 · see citing works
Self-citationThe crucial regulatory role of type I interferon in inflammatory diseases
Ji, L., Li, T., Chen, H., Yang, Y., Liu, J., Liu, J., Qiao, W., & Chen, H. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01188-z · Cited by 101 · see citing works
Self-citationISG15 in cancer: Beyond ubiquitin-like protein
Han, H. G., Moon, H. W., & Jeon, Y. J. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.09.007 · Cited by 98 · see citing works
Beyond ISGlylation: Functions of Free Intracellular and Extracellular ISG15
dos Santos, P. F., & Mansur, D. S. (2017) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2016.0103 · Cited by 97 · see citing works
Incomplete penetrance in primary immunodeficiency: a skeleton in the closet
Gruber, C., & Bogunovic, D. (2020) · Human Genetics · doi:10.1007/s00439-020-02131-9 · Cited by 97 · see citing works
Self-citationUnderstanding Human Autoimmunity and Autoinflammation Through Transcriptomics
Banchereau, R., Cepika, A., Banchereau, J., & Pascual, V. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052225 · Cited by 94 · see citing works
Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions
Martín-Fernández, M., García‐Morato, M. B., Gruber, C. N., Loza, S. M. M., Malik, M. N. H., Alsohime, F., Alakeel, A., Valdéz, R., Buta, S., Buda, G., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107633 · Cited by 93 · see citing works
Self-citationAcute microglia ablation induces neurodegeneration in the somatosensory system
Rubino, S. J., Mayo, L., Wimmer, I., Siedler, V., Brunner, F., Hametner, S., Madi, A., Lanser, A., Moreira, T., Donnelly, D., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05929-4 · Cited by 91 · see citing works
Type I Interferonopathies in Children: An Overview
d’Angelo, D. M., Filippo, P. D., Breda, L., & Chiarelli, F. (2021) · Frontiers in Pediatrics · doi:10.3389/fped.2021.631329 · Cited by 89 · see citing works
Iwata, S., Mikami, Y., Sun, H., Brooks, S. R., Jankovic, D. L., Hirahara, K., Onodera, A., Shih, H., Kawabe, T., Jiang, K., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.05.005 · Cited by 89 · see citing works
Ott, N., Faletti, L. E., Heeg, M., Andreani, V., & Grimbacher, B. (2023) · Journal of Clinical Immunology · doi:10.1007/s10875-023-01483-x · Cited by 87 · see citing works
Roles of unphosphorylated ISGF3 in HCV infection and interferon responsiveness
Sung, P. S., Cheon, H., Cho, C. H., Hong, S.-H., Park, D. Y., Seo, H.-I., Park, S., Yoon, S. K., Stark, G. R., & Shin, E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1513341112 · Cited by 84 · see citing works
Østvik, A. E., Svendsen, T. D., Granlund, A. V. B., Doseth, B., Skovdahl, H. K., Bakke, I., Thorsvik, S., Afroz, W., Walaas, G. A., Mollnes, T. E., et al. (2020) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjaa022 · Cited by 84 · see citing works
Chen, R., Xiao, Z., Yan, X., Han, P., Liang, F.-Y., Wang, J., Yu, S., Zhang, T.-Z., Chen, S.-Q., Zhong, Q., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.594775 · Cited by 84 · see citing works
Inborn errors of immunity: an expanding universe of disease and genetic architecture
Akalu, Y. T., & Bogunovic, D. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00656-z · Cited by 82 · see citing works
Self-citationHERC5 and the ISGylation Pathway: Critical Modulators of the Antiviral Immune Response
Mathieu, N. A., Paparisto, E., Barr, S. D., & Spratt, D. E. (2021) · Viruses · doi:10.3390/v13061102 · Cited by 81 · see citing works
RNA degradation in antiviral immunity and autoimmunity
Rigby, R. E., & Rehwinkel, J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.001 · Cited by 80 · see citing works
A partial form of inherited human USP18 deficiency underlies infection and inflammation
Martín-Fernández, M., Buta, S., Voyer, T. L., Li, Z., Dynesen, L. T., Vuillier, F., Franklin, L., Ailal, F., Amancio, A. M. T. D. S., Malle, L., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20211273 · Cited by 80 · see citing works
Self-citationExpansion of interferon inducible gene pool via USP18 inhibition promotes cancer cell pyroptosis
Arimoto, K., Miyauchi, S., Troutman, T. D., Zhang, Y., Liu, M., Stoner, S. A., Davis, A. G., Fan, J.-B., Huang, Y.-J., Yan, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-35348-5 · Cited by 80 · see citing works
Self-citationShen, M., Duan, C., Xie, C., Wang, H., Li, Z., Li, B., & Wang, T. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.962393 · Cited by 79 · see citing works
Self-citation
- Authors
- Zhang, X., Bogunovic, D., Payelle-Brogard, B., Francois-Newton, V., Speer, S. D., Yuan, C., Volpi, S., Li, Z., Sanal, O., Mansouri, D., Tezcan, I., Rice, G. I., Chen, C., Mansouri, N., Mahdaviani, S. A., Itan, Y., Boisson, B., Okada, S., Zeng, L., Wang, X., Jiang, H., Liu, W., Han, T., Liu, D., Ma, T., Wang, B., Liu, M., Liu, J.-Y., Wang, Q. K., Yalnizoglu, D., Radoshevich, L., Uzé, G., Gros, P., Rozenberg, F., Zhang, S.-Y., Jouanguy, E., Bustamante, J., García-Sastre, A., Abel, L., Lebon, P., Notarangelo, L. D., Crow, Y. J., Boisson-Dupuis, S., Casanova, J.-L., & Pellegrini, S.
- Affiliations
- Huazhong University of Science and Technology (CN)
- Rockefeller University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Boston Children's Hospital (US)
- Centre National de la Recherche Scientifique (FR)
- Masih Daneshvari Hospital (IR)
- Manchester Academic Health Science Centre (GB)
- BGI Group (China) (CN)
- Hubei Provincial Women and Children's Hospital (CN)
- Cleveland Clinic (US)
- Institut Pasteur (FR)
- McGill University (CA)
- Université Paris Descartes (FR)
- Hôpital Necker-Enfants Malades (FR)
- Inserm (FR)
- Corresponding author
- Bogunovic, Dusan
- ORCID
- Zhang, Xianqin
- Bogunovic, Dusan
- Speer, Scott D.
- Yuan, Chao
- Volpi, Stefano
- Li, Zhi
- Mansouri, Davood
- Rice, Gillian I.
- Mansouri, Nahal
- Mahdaviani, Seyed Alireza
- Itan, Yuval
- Boisson, Bertrand
- Okada, Satoshi
- Zeng, Lu
- Wang, Xing
- Jiang, Hui
- Han, Tiantian
- Liu, Delin
- Ma, Tao
- Liu, Mugen
- Wang, Qing K.
- Radoshevich, Lilliana
- Uzé, Gilles
- Gros, Philippe
- Rozenberg, Flore
- Zhang, Shen-Ying
- Jouanguy, Emmanuelle
- Bustamante, Jacinta
- Abel, Laurent
- Notarangelo, Luigi D.
- Crow, Yanick J.
- Casanova, Jean-Laurent
- Pellegrini, Sandra
- Venue
- Nature
- Published
- 2014-10-12
- Volume
- 517
- Issue
- 7532
- Pages
- 89-93
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4303590
- OpenAlex
- W1601709990
- Cited by
- 558
- References
- 31
- Citations by year
- 2026: 45 · 2025: 36 · 2024: 56 · 2023: 57 · 2022: 43 · 2021: 49 · 2020: 57 · 2019: 35 · 2018: 36 · 2017: 58 · 2016: 43 · 2015: 42 · 2014: 1
- FWCI
- 20.31
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-02-11)
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion, other-oa)
- IRIS (submittedVersion)
- Hacettepe University Institutional Repository (hacettepe.edu.tr) (submittedVersion, other-oa)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- European Commission (200732, 241779, 2007–2013, FP7 2007-2013, FP7/2007, 223608)
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Greater Manchester Comprehensive Local Research Network
- National Institutes of Health (UL1TR000043, FP7/2007-2013)
- Manchester Biomedical Research Centre
- Japan Society for the Promotion of Science (25713039, 25670477)
- National Institute of Allergy and Infectious Diseases (P01AI076210, R01AI035237, P01AI090935, 1PO1AI076210-01A1, U19AI083025, R00AI106942, R37AI095983)
- National Center for Research Resources
- National Center for Advancing Translational Sciences
- FP7 Ideas: European Research Council (309449)
- CHIST-ERA
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- ISG15, USP18, type I interferon, autoinflammation, Aicardi-Goutières syndrome, interferonopathies, ISGylation, ubiquitin-like proteins, mycobacterial infection, interferon-gamma
- MeSH terms
- Adolescent, Alleles, Child, Female, Gene Expression Regulation, Humans, Inflammation, Interferon Type I, Male, Pedigree, Endopeptidases, Ubiquitins, Viruses, Signal Transduction, Cytokines, Intracellular Space, Ubiquitin Thiolesterase, S-Phase Kinase-Associated Proteins, Ubiquitination
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
