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-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. © 2014 fitzgerald et al.; licensee biomed central ltd.