Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis.

2.50
Hdl Handle:
http://hdl.handle.net/10033/615994
Title:
Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis.
Authors:
Khorooshi, Reza; Mørch, Marlene Thorsen; Holm, Thomas Hellesøe; Berg, Carsten Tue; Dieu, Ruthe Truong; Dræby, Dina; Issazadeh-Navikas, Shohreh; Weiss, Siegfried ( 0000-0002-5276-8658 ) ; Lienenklaus, Stefan; Owens, Trevor
Abstract:
The 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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Induction 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.
Journal:
Acta neuropathologica
Issue Date:
Jul-2015
URI:
http://hdl.handle.net/10033/615994
DOI:
10.1007/s00401-015-1418-z
PubMed ID:
25869642
Type:
Article
Language:
en
ISSN:
1432-0533
Appears in Collections:
publications of the research group molecular Immunology (MOLI)

Full metadata record

DC FieldValue Language
dc.contributor.authorKhorooshi, Rezaen
dc.contributor.authorMørch, Marlene Thorsenen
dc.contributor.authorHolm, Thomas Hellesøeen
dc.contributor.authorBerg, Carsten Tueen
dc.contributor.authorDieu, Ruthe Truongen
dc.contributor.authorDræby, Dinaen
dc.contributor.authorIssazadeh-Navikas, Shohrehen
dc.contributor.authorWeiss, Siegfrieden
dc.contributor.authorLienenklaus, Stefanen
dc.contributor.authorOwens, Trevoren
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.en
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

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