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

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-beta 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.

The Edinburgh Critical Edition of the Selected Writings of Andrew Lang: volume 1

This is the first critical edition of the works of Andrew Lang (1844-1912), the Scottish writer whose enormous output spanned the whole range of late nineteenth century intellectual culture. Neglected since his death, partly because of the diversity of his interests and the volume of his writing, his cultural centrality and the interdisciplinary nature of his work make him a vital figure for contemporary scholars. This volume covers his work in anthropology, including that on fairy tale, folklore, the origins of religion, and psychical research.