Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Khorooshi, RezaMørch, Marlene Thorsen
Holm, Thomas Hellesøe
Berg, Carsten Tue
Dieu, Ruthe Truong
Dræby, Dina
Issazadeh-Navikas, Shohreh
Weiß, Siegfried
Lienenklaus, Stefan
Owens, Trevor
Issue Date
2015-07
Metadata
Show full item recordAbstract
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.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.Affiliation
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.Journal
Acta neuropathologicaPubMed ID
25869642Type
ArticleLanguage
enISSN
1432-0533ae974a485f413a2113503eed53cd6c53
10.1007/s00401-015-1418-z
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
Related articles
- High interleukin-10 expression within the central nervous system may be important for initiation of recovery of Dark Agouti rats from experimental autoimmune encephalomyelitis.
- Authors: Blaževski J, Petković F, Momčilović M, Jevtic B, Miljković D, Mostarica Stojković M
- Issue date: 2013 Sep
- Ulinastatin attenuates experimental autoimmune encephalomyelitis by enhancing anti-inflammatory responses.
- Authors: Feng M, Shu Y, Yang Y, Zheng X, Li R, Wang Y, Dai Y, Qiu W, Lu Z, Hu X
- Issue date: 2014 Jan
- Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system.
- Authors: Prinz M, Schmidt H, Mildner A, Knobeloch KP, Hanisch UK, Raasch J, Merkler D, Detje C, Gutcher I, Mages J, Lang R, Martin R, Gold R, Becher B, Brück W, Kalinke U
- Issue date: 2008 May
- Astrocyte response to IFN-γ limits IL-6-mediated microglia activation and progressive autoimmune encephalomyelitis.
- Authors: Savarin C, Hinton DR, Valentin-Torres A, Chen Z, Trapp BD, Bergmann CC, Stohlman SA
- Issue date: 2015 Apr 22
- Activation of CB2 receptor is required for the therapeutic effect of ABHD6 inhibition in experimental autoimmune encephalomyelitis.
- Authors: Wen J, Ribeiro R, Tanaka M, Zhang Y
- Issue date: 2015 Dec