liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord
Medical University of Vienna, Austria.
Medical University of Vienna, Austria.
Medical University of Vienna, Austria.
Medical University of Vienna, Austria.
Show others and affiliations
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, e0151244- p.Article in journal (Refereed) PublishedText
Abstract [en]

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.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE , 2016. Vol. 11, no 3, e0151244- p.
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-127436DOI: 10.1371/journal.pone.0151244ISI: 000372582800051PubMedID: 26990978OAI: diva2:925255

Funding Agencies|Austrian Science Fund [P25240-B24]; Austrian Ministry of Science, Research and Economy (BIGWIG-MS); Ministry of Education, Culture, Sports, Science and Technology of Japan; Alumni Association of Saitama Medical University

Available from: 2016-05-01 Created: 2016-04-26 Last updated: 2016-05-17

Open Access in DiVA

fulltext(22576 kB)27 downloads
File information
File name FULLTEXT01.pdfFile size 22576 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Dahle, Charlotte
By organisation
Division of Neuro and Inflammation ScienceDepartment of Clinical Immunology and Transfusion MedicineFaculty of Medicine and Health Sciences
In the same journal
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 27 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 107 hits
ReferencesLink to record
Permanent link

Direct link