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

Fitzgerald DC, O'Brien K, Young A, Fonseca-Kelly Z, Rostami A, Gran B.
Source: Journal of Neuroinflammation
Publication Date: (2014)
Issue: 11: 130
Research Area:
Immunotherapy / Hematology
Cells used in publication:
T cell, mouse, stim
Species: mouse
Tissue Origin: blood
Culture Media:

Mouse spleens were harvested from wild-type (WT) and irf3-/- mice, and single-cell suspensions were prepared following erythrocyte lysis. Cells were cultured at a density of 2 × 106 cells/ml in X-VIVO 15 medium (Lonza, Walkersville, MD, USA) and activated with anti-CD3/anti-CD28 antibodies or with MOG35–55 (25 µg/ml) 


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-ß 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.