Journal Article

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

Weiss, Siegfried, Khorooshi, Reza, Dræby, Dina, Mørch, Marlene Thorsen, Lienenklaus, Stefan, Berg, Carsten Tue, Owens, Trevor, Holm, Thomas Hellesøe, Issazadeh-Navikas, Shohreh, Dieu, Ruthe Truong

2015

Overview

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,Springer,Springer Nature B.V
• Subject: Animals / Astrocytes - drug effects / Astrocytes - immunology / Astrocytes - pathology / Biological response modifiers / Brain - drug effects / Brain - immunology / Brain - pathology / Central nervous system / Chemokine CXCL10 - metabolism / Chemokines / Encephalomyelitis / Encephalomyelitis, Autoimmune, Experimental - drug therapy / Encephalomyelitis, Autoimmune, Experimental - immunology / Encephalomyelitis, Autoimmune, Experimental - pathology / Health aspects / Immunology / Inflammation / Interferon / Interferon-alpha - genetics / Interferon-alpha - metabolism / Interferon-beta - genetics / Interferon-beta - metabolism / Laboratories / Leukocytes - drug effects / Leukocytes - pathology / Leukocytes - physiology / Medicine / Medicine & Public Health / Meninges - drug effects / Meninges - immunology / Meninges - pathology / Mice, Inbred C57BL / Mice, Transgenic / Microglia - drug effects / Microglia - pathology / Microglia - physiology / Multiple sclerosis / Nervous system / Neurophysiology / Neuroprotective Agents - pharmacology / Neurosciences / Original Paper / Pathology / Poly I-C - pharmacology / Random Allocation / Receptor, Interferon alpha-beta - genetics / Receptor, Interferon alpha-beta - metabolism / Spinal Cord - drug effects / Spinal Cord - immunology / Spinal Cord - pathology