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

Denise Fitzgerald, Kate O'Brien, Andrew Young, Zoe Fonseca-Kelly, Abdolmohamad Rostami, Bruno Gran

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


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.
Original languageEnglish
JournalJournal of Neuroinflammation
Issue number130
Publication statusPublished - 28 Jul 2014


  • Multiple Sclerosis
  • IRF3
  • Th17
  • EAE


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