Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis.
dc.contributor.author | Khorooshi, Reza | |
dc.contributor.author | Mørch, Marlene Thorsen | |
dc.contributor.author | Holm, Thomas Hellesøe | |
dc.contributor.author | Berg, Carsten Tue | |
dc.contributor.author | Dieu, Ruthe Truong | |
dc.contributor.author | Dræby, Dina | |
dc.contributor.author | Issazadeh-Navikas, Shohreh | |
dc.contributor.author | Weiß, Siegfried | |
dc.contributor.author | Lienenklaus, Stefan | |
dc.contributor.author | Owens, Trevor | |
dc.date.accessioned | 2016-07-13T08:04:58Z | |
dc.date.available | 2016-07-13T08:04:58Z | |
dc.date.issued | 2015-07 | |
dc.identifier.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. | en |
dc.identifier.issn | 1432-0533 | |
dc.identifier.pmid | 25869642 | |
dc.identifier.doi | 10.1007/s00401-015-1418-z | |
dc.identifier.uri | http://hdl.handle.net/10033/615994 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | Animals | en |
dc.subject.mesh | Astrocytes | en |
dc.subject.mesh | Brain | en |
dc.subject.mesh | Chemokine CXCL10 | en |
dc.subject.mesh | Encephalomyelitis, Autoimmune, Experimental | en |
dc.subject.mesh | Interferon-alpha | en |
dc.subject.mesh | Interferon-beta | en |
dc.subject.mesh | Leukocytes | en |
dc.subject.mesh | Meninges | en |
dc.subject.mesh | Mice, Inbred C57BL | en |
dc.subject.mesh | Mice, Transgenic | en |
dc.subject.mesh | Microglia | en |
dc.subject.mesh | Neuroprotective Agents | en |
dc.subject.mesh | Poly I-C | en |
dc.subject.mesh | Random Allocation | en |
dc.subject.mesh | Receptor, Interferon alpha-beta | en |
dc.subject.mesh | Spinal Cord | en |
dc.title | Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis. | en |
dc.type | Article | en |
dc.contributor.department | Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. | en |
dc.identifier.journal | Acta neuropathologica | en |
refterms.dateFOA | 2018-06-13T17:04:45Z | |
html.description.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. |