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

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 sh...

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Main Authors:	Khorooshi, Reza, Mørch, Marlene Thorsen, Holm, Thomas Hellesøe, Berg, Carsten Tue, Dieu, Ruthe Truong, Dræby, Dina, Issazadeh-Navikas, Shohreh, Weiss, Siegfried, Lienenklaus, Stefan, Owens, Trevor
Format:	Online
Language:	English
Published:	Springer Berlin Heidelberg 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469095/

id	pubmed-4469095
recordtype	oai_dc
spelling	pubmed-44690952015-06-17 Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis Khorooshi, Reza Mørch, Marlene Thorsen Holm, Thomas Hellesøe Berg, Carsten Tue Dieu, Ruthe Truong Dræby, Dina Issazadeh-Navikas, Shohreh Weiss, Siegfried Lienenklaus, Stefan Owens, Trevor Original Paper 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. Springer Berlin Heidelberg 2015-04-14 2015 /pmc/articles/PMC4469095/ /pubmed/25869642 http://dx.doi.org/10.1007/s00401-015-1418-z Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Khorooshi, Reza Mørch, Marlene Thorsen Holm, Thomas Hellesøe Berg, Carsten Tue Dieu, Ruthe Truong Dræby, Dina Issazadeh-Navikas, Shohreh Weiss, Siegfried Lienenklaus, Stefan Owens, Trevor
spellingShingle	Khorooshi, Reza Mørch, Marlene Thorsen Holm, Thomas Hellesøe Berg, Carsten Tue Dieu, Ruthe Truong Dræby, Dina Issazadeh-Navikas, Shohreh Weiss, Siegfried Lienenklaus, Stefan Owens, Trevor Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis
author_facet	Khorooshi, Reza Mørch, Marlene Thorsen Holm, Thomas Hellesøe Berg, Carsten Tue Dieu, Ruthe Truong Dræby, Dina Issazadeh-Navikas, Shohreh Weiss, Siegfried Lienenklaus, Stefan Owens, Trevor
author_sort	Khorooshi, Reza
title	Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis
title_short	Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis
title_full	Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis
title_fullStr	Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis
title_full_unstemmed	Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis
title_sort	induction of endogenous type i interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis
description	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.
publisher	Springer Berlin Heidelberg
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469095/
_version_	1613236261519097856

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

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