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dc.contributor.authorFletcher, Jeanen
dc.contributor.authorBasdeo, Shareeen
dc.contributor.authorMills, Kingstonen
dc.date.accessioned2011-04-19T14:17:37Z
dc.date.available2011-04-19T14:17:37Z
dc.date.issued2011en
dc.date.submitted2011en
dc.identifier.citationCheryl M. Sweeney, Roisin Lonergan, Sharee A. Basdeo, Katie Kinsella, Lara S. Dungan, Sarah C. Higgins, Patrick J. Kelly, Lisa Costelloe, Niall Tubridy, Kingston H.G. Mills, Jean M. Fletcher, IL-27 mediates the response to IFN beta therapy in multiple sclerosis patients by inhibiting Th17 cells, Brain, Behavior and Immunity, 25, 6, 2011, 1170-1181en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/54935
dc.descriptionPUBLISHEDen
dc.description.abstractInterferon (IFN)-? is a commonly used therapy for relapsing remitting multiple sclerosis (RRMS). However its protective mechanism is still unclear and the failure of many patients to respond has not been explained. We have found that IFN-? suppressed IL-23 and IL-1? production and increased IL-10 production by human dendritic cells (DC) activated with the TLR2 and dectin-1 agonist zymosan. Furthermore, IFN-? impaired the ability of DC to promote IL-17 production by CD4+ T cells, but did not affect IFN-? production. IFN-? induced IL-27 expression by DC, and neutralisation of IL-27 abrogated the suppressive effects of IFN-? on zymosan-induced IL-1 and IL-23 production and the generation of Th17 cells in vitro. Complementary in vivo studies in a mouse model showed that treatment with IFN-? enhanced expression of IL-27, and reduced IL-17 in the CNS and periphery and attenuated the clinical signs of experimental autoimmune encephalomyelitis (EAE). In addition, the significant suppressive effect of IFN-? on the ability of DC to promote Th17 cells was lost in cells from IL-27 receptor deficient mice. Finally, we showed that PBMC from non-responder RRMS patients produced significantly less IL-27 in response to IFN-? than patients who responded to IFN-? therapy. Our findings suggest that IFN-? mediates its therapeutic effects in MS at least in part via the induction of IL-27, and that IL-27 may represent an alternative therapy for MS patients that do not respond to IFN-?.en
dc.description.sponsorshipThe authors would like to thank Cliona O?Farrelly for facilitating this study and for helpful discussions. This work was supported by grants to KM from Science Foundation Ireland. JF was supported by a Postdoctoral Fellowship from the Irish Health Research Board and a Starting Investigator Research Grant from Science Foundation Ireland.en
dc.format.extent1170-1181en
dc.language.isoenen
dc.relation.ispartofseriesBrain, Behavior and Immunityen
dc.relation.ispartofseries25en
dc.relation.ispartofseries6en
dc.rightsYen
dc.subjectImmunologyen
dc.subjectmultiple sclerosisen
dc.subjectInterferon (IFN)-?en
dc.subjectTh17en
dc.subjectIL-27en
dc.subjectdendritic cellen
dc.titleIL-27 mediates the response to IFN beta therapy in multiple sclerosis patients by inhibiting Th17 cellsen
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.contributor.sponsorHealth Research Board (HRB)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/millsken
dc.identifier.peoplefinderurlhttp://people.tcd.ie/fletchjen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/sbasdeoen
dc.identifier.rssinternalid71883en
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.subject.TCDThemeNeuroscienceen
dc.identifier.rssurihttp://dx.doi.org/10.1016/j.bbi.2011.03.007en
dc.identifier.orcid_id0000-0003-3646-8222en


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