Interferon regulatory factor-7 modulates experimental autoimmune encephalomyelitis in miceReport as inadecuate




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Journal of Neuroinflammation

, 8:181

First Online: 23 December 2011Received: 05 July 2011Accepted: 23 December 2011

Abstract

BackgroundMultiple 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.

MethodsThe 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.

ResultsIRF7 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.

ConclusionTogether, our findings suggest that IRF7 signaling is critical for regulation of inflammatory responses in the CNS.

KeywordsIRF7 type I IFN EAE inflammation central nervous system chemokines cytokines List of abbreviationsAPCallophycocyanin

CNScentral nervous system

EAEexperimental autoimmune encephalomyelitis

IRF7Interferon regulatory factor 7

IFNInterferon

IL-1βinterleukin-1β

IFNARtype I interferon receptor

LNlymph node

MOGmyelin oligodendrocyte glycoprotein

MSmultiple sclerosis

PEphycoerythrin.

Electronic supplementary materialThe online version of this article doi:10.1186-1742-2094-8-181 contains supplementary material, which is available to authorized users.

Mohammad Salem, Jyothi T Mony contributed equally to this work.

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Author: Mohammad Salem - Jyothi T Mony - Morten Løbner - Reza Khorooshi - Trevor Owens

Source: https://link.springer.com/







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