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dc.contributor.authordos Santos, Paula Fernandesen
dc.contributor.authorVan Weyenbergh, Johanen
dc.contributor.authorDelgobo, Muriloen
dc.contributor.authorPatricio, Daniel de Oliveiraen
dc.contributor.authorFerguson, Brianen
dc.contributor.authorGUABIRABA, RODRIGOen
dc.contributor.authorDierckx, Timen
dc.contributor.authorMENEZES, Soraya Maria Mariaen
dc.contributor.authorBafica, Andreen
dc.contributor.authorMansur, Danielen
dc.date.accessioned2019-03-27T00:30:14Z
dc.date.available2019-03-27T00:30:14Z
dc.date.issued2017-07-21en
dc.identifier.issn1550-6606
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/290852
dc.description.abstractInterferon stimulated gene 15 (ISG15) deficiency in humans leads to severe interferonopathies and mycobacterial disease, the latter being previously attributed to its extracellular cytokine-like activity. Here, we demonstrate a novel role for secreted ISG15 as an IL-10 inducer, unique to primary human monocytes. Employing ex vivo systems analysis of human transcriptome datasets, we observed a significant correlation of ISG15-induced monocyte IL-10 and lymphocyte IFNγ expression. This effect was associated with p38 MAPK and PI3K signalling in healthy volunteers. The specificity and MAPK/PI3K-dependence of ISG15-induced monocyte IL-10 production was confirmed in vitro using CRISPR/Cas9 knockout and pharmacological inhibitors. Moreover, this ISG15/IL10 axis was amplified in leprosy but disrupted in human active tuberculosis (TB) patients. Importantly, ISG15 strongly correlated with inflammation and disease severity during active TB. In conclusion, this study identifies a novel anti-inflammatory ISG15/IL-10 myeloid axis that is disrupted in active TB, revealing a potential biomarker for disease severity in this major human disease.
dc.publisherAmerican Association of Immunologists
dc.rights
dc.rights.uri
dc.titleISG15 induces IL-10 production in human monocytes and is a biomarker of disease severity during active tuberculosisen
dc.typeArticle
prism.publicationDate2017en
dc.identifier.doi10.17863/CAM.38046
pubs.declined2019-03-18T14:52:22.642+0000
dcterms.dateAccepted2017-12-11en
rioxxterms.versionofrecord10.1101/166553en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-07-21en
dc.contributor.orcidVan Weyenbergh, Johan [0000-0003-3234-8426]
dc.contributor.orcidFerguson, Brian [0000-0002-6873-1032]
dc.contributor.orcidDierckx, Tim [0000-0002-1969-7974]
dc.contributor.orcidMansur, Daniel [0000-0001-6773-9334]
rioxxterms.typeJournal Article/Reviewen
rioxxterms.freetoread.startdate2018-07-21


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