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

Journal of Neuroinflammation

Bruno Gran¹  Abdolmohamad Rostami³  Zoe Fonseca-Kelly³  Andrew Young²  Kate O’Brien¹  Denise C Fitzgerald² 

[1] Clinical Neurology Research Group, Division of Clinical Neuroscience, University of Nottingham School of Medicine, C Floor South Block, Queen’s Medical Centre, Nottingham NG7 2UH, UK;Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK;Department of Neurology, Thomas Jefferson University, 909 Walnut Street, 2nd Floor, COB Bldg., Philadelphia PA 19107, USA

关键词: Th17;    IRF3;    Inflammation;    EAE;    Autoimmune;   

Others  :  1151213
DOI  :  10.1186/1742-2094-11-130

 received in 2014-04-03, accepted in 2014-07-08,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Fitzgerald et al.; licensee BioMed Central Ltd.

【 图 表 】

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