title: Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord.
abstract: Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN.
authors.affiliation: Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria.
authors.forename: Satoru
authors.initials: S
authors.lastname: Oji
authors.affiliation: Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Nicolussi
authors.affiliation: Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kaufmann
authors.affiliation: Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria.
authors.forename: Bleranda
authors.initials: B
authors.lastname: Zeka
authors.affiliation: Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schanda
authors.affiliation: Departments of Multiple Sclerosis Therapeutics and Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.affiliation: Department of Neurology, University of Southern Denmark, Odense, Denmark.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Illes
authors.affiliation: Department of Clinical Immunology and Transfusion Medicine and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Dahle
authors.affiliation: Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.affiliation: Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria.
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.affiliation: Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Bradl
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001812:Blood-Brain Barrier / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D017628:Microglia / Q000276:immunology / Q000473:pathology; D009471:Neuromyelitis Optica / Q000276:immunology* / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D007370:Interferon Type I