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dc.contributor.authorKhorooshi, Reza
dc.contributor.authorMørch, Marlene Thorsen
dc.contributor.authorHolm, Thomas Hellesøe
dc.contributor.authorBerg, Carsten Tue
dc.contributor.authorDieu, Ruthe Truong
dc.contributor.authorDræby, Dina
dc.contributor.authorIssazadeh-Navikas, Shohreh
dc.contributor.authorWeiß, Siegfried
dc.contributor.authorLienenklaus, Stefan
dc.contributor.authorOwens, Trevor
dc.date.accessioned2016-07-13T08:04:58Z
dc.date.available2016-07-13T08:04:58Z
dc.date.issued2015-07
dc.identifier.citationInduction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis. 2015, 130 (1):107-18 Acta Neuropathol.en
dc.identifier.issn1432-0533
dc.identifier.pmid25869642
dc.identifier.doi10.1007/s00401-015-1418-z
dc.identifier.urihttp://hdl.handle.net/10033/615994
dc.description.abstractThe Type I interferons (IFN), beta (IFN-β) and the alpha family (IFN-α), act through a common receptor and have anti-inflammatory effects. IFN-β is used to treat multiple sclerosis (MS) and is effective against experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Mice with EAE show elevated levels of Type I IFNs in the central nervous system (CNS), suggesting a role for endogenous Type I IFN during inflammation. However, the therapeutic benefit of Type I IFN produced in the CNS remains to be established. The aim of this study was to examine whether experimentally induced CNS-endogenous Type I IFN influences EAE. Using IFN-β reporter mice, we showed that direct administration of polyinosinic-polycytidylic acid (poly I:C), a potent inducer of IFN-β, into the cerebrospinal fluid induced increased leukocyte numbers and transient upregulation of IFN-β in CD45/CD11b-positive cells located in the meninges and choroid plexus, as well as enhanced IFN-β expression by parenchymal microglial cells. Intrathecal injection of poly I:C to mice showing first symptoms of EAE substantially increased the normal disease-associated expression of IFN-α, IFN-β, interferon regulatory factor-7 and IL-10 in CNS, and disease worsening was prevented for as long as IFN-α/β was expressed. In contrast, there was no therapeutic effect on EAE in poly I:C-treated IFN receptor-deficient mice. IFN-dependent microglial and astrocyte response included production of the chemokine CXCL10. These results show that Type I IFN induced within the CNS can play a protective role in EAE and highlight the role of endogenous type I IFN in mediating neuroprotection.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshAstrocytesen
dc.subject.meshBrainen
dc.subject.meshChemokine CXCL10en
dc.subject.meshEncephalomyelitis, Autoimmune, Experimentalen
dc.subject.meshInterferon-alphaen
dc.subject.meshInterferon-betaen
dc.subject.meshLeukocytesen
dc.subject.meshMeningesen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Transgenicen
dc.subject.meshMicrogliaen
dc.subject.meshNeuroprotective Agentsen
dc.subject.meshPoly I-Cen
dc.subject.meshRandom Allocationen
dc.subject.meshReceptor, Interferon alpha-betaen
dc.subject.meshSpinal Corden
dc.titleInduction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalActa neuropathologicaen
refterms.dateFOA2018-06-13T17:04:45Z
html.description.abstractThe Type I interferons (IFN), beta (IFN-β) and the alpha family (IFN-α), act through a common receptor and have anti-inflammatory effects. IFN-β is used to treat multiple sclerosis (MS) and is effective against experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Mice with EAE show elevated levels of Type I IFNs in the central nervous system (CNS), suggesting a role for endogenous Type I IFN during inflammation. However, the therapeutic benefit of Type I IFN produced in the CNS remains to be established. The aim of this study was to examine whether experimentally induced CNS-endogenous Type I IFN influences EAE. Using IFN-β reporter mice, we showed that direct administration of polyinosinic-polycytidylic acid (poly I:C), a potent inducer of IFN-β, into the cerebrospinal fluid induced increased leukocyte numbers and transient upregulation of IFN-β in CD45/CD11b-positive cells located in the meninges and choroid plexus, as well as enhanced IFN-β expression by parenchymal microglial cells. Intrathecal injection of poly I:C to mice showing first symptoms of EAE substantially increased the normal disease-associated expression of IFN-α, IFN-β, interferon regulatory factor-7 and IL-10 in CNS, and disease worsening was prevented for as long as IFN-α/β was expressed. In contrast, there was no therapeutic effect on EAE in poly I:C-treated IFN receptor-deficient mice. IFN-dependent microglial and astrocyte response included production of the chemokine CXCL10. These results show that Type I IFN induced within the CNS can play a protective role in EAE and highlight the role of endogenous type I IFN in mediating neuroprotection.


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