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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2011

Open Access 01-12-2011 | Research

Interferon regulatory factor-7 modulates experimental autoimmune encephalomyelitis in mice

Authors: Mohammad Salem, Jyothi T Mony, Morten Løbner, Reza Khorooshi, Trevor Owens

Published in: Journal of Neuroinflammation | Issue 1/2011

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Abstract

Background

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) with unknown etiology. Interferon-β (IFN-β), a member of the type I IFN family, is used as a therapeutic for MS and the IFN signaling pathway is implicated in MS susceptibility. Interferon regulatory factor 7 (IRF7) is critical for the induction and positive feedback regulation of type I IFN. To establish whether and how endogenous type I IFN signaling contributes to disease modulation and to better understand the underlying mechanism, we examined the role of IRF7 in the development of MS-like disease in mice.

Methods

The role of IRF7 in development of EAE was studied by immunizing IRF7-KO and C57BL/6 (WT) mice with myelin oligodendrocyte glycoprotein using a standard protocol for the induction of EAE. We measured leukocyte infiltration and localization in the CNS using flow cytometric analysis and immunohistochemical procedures. We determined levels of CD3 and selected chemokine and cytokine gene expression by quantitative real-time PCR.

Results

IRF7 gene expression increased in the CNS as disease progressed. IRF7 message was localized to microglia and infiltrating leukocytes. Furthermore, IRF7-deficient mice developed more severe disease. Flow cytometric analysis showed that the extent of leukocyte infiltration into the CNS was higher in IRF7-deficient mice with significantly higher number of infiltrating macrophages and T cells, and the distribution of infiltrates within the spinal cord was altered. Analysis of cytokine and chemokine gene expression by quantitative real-time PCR showed significantly greater increases in CCL2, CXCL10, IL-1β and IL17 gene expression in IRF7-deficient mice compared with WT mice.

Conclusion

Together, our findings suggest that IRF7 signaling is critical for regulation of inflammatory responses in the CNS.
Appendix
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Metadata
Title
Interferon regulatory factor-7 modulates experimental autoimmune encephalomyelitis in mice
Authors
Mohammad Salem
Jyothi T Mony
Morten Løbner
Reza Khorooshi
Trevor Owens
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2011
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-8-181

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