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Journal of Neuroinflammation

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Open Access 01-12-2014 | Research

Interferon regulatory factor (IRF) 3 is critical for the development of experimental autoimmune encephalomyelitis

Authors: Denise C Fitzgerald, Kate O’Brien, Andrew Young, Zoe Fonseca-Kelly, Abdolmohamad Rostami, Bruno Gran

Published in: Journal of Neuroinflammation | Issue 1/2014

Abstract

Background

Experimental autoimmune encephalomyelitis (EAE) is an animal model of autoimmune inflammatory demyelination that is mediated by Th1 and Th17 cells. The transcription factor interferon regulatory factor 3 (IRF3) is activated by pathogen recognition receptors and induces interferon-β production.

Methods

To determine the role of IRF3 in autoimmune inflammation, we immunised wild-type (WT) and irf3 ^−/− mice to induce EAE. Splenocytes from WT and irf3 ^−/− mice were also activated in vitro in Th17-polarising conditions.

Results

Clinical signs of disease were significantly lower in mice lacking IRF3, with reduced Th1 and Th17 cells in the central nervous system. Peripheral T-cell responses were also diminished, including impaired proliferation and Th17 development in irf3 ^−/− mice. Myelin-reactive CD4⁺ cells lacking IRF3 completely failed to transfer EAE in Th17-polarised models as did WT cells transferred into irf3 ^−/− recipients. Furthermore, IRF3 deficiency in non-CD4⁺ cells conferred impairment of Th17 development in antigen-activated cultures.

Conclusion

These data show that IRF3 plays a crucial role in development of Th17 responses and EAE and warrants investigation in human multiple sclerosis.

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Title: Interferon regulatory factor (IRF) 3 is critical for the development of experimental autoimmune encephalomyelitis
Authors: Denise C Fitzgerald
Kate O’Brien
Andrew Young
Zoe Fonseca-Kelly
Abdolmohamad Rostami
Bruno Gran
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2014
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-11-130

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Interferon regulatory factor (IRF) 3 is critical for the development of experimental autoimmune encephalomyelitis

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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