title: Interferon regulatory factor (IRF) 3 is critical for the development of experimental autoimmune encephalomyelitis.
abstract: 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.
  
  
  CONCLUSIONS
  These data show that IRF3 plays a crucial role in development of Th17 responses and EAE and warrants investigation in human multiple sclerosis.
authors: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK. d.fitzgerald@qub.ac.uk.
authors: Denise C
authors: DC
authors: Fitzgerald
authors: Kate
authors: K
authors: O'Brien
authors: Andrew
authors: A
authors: Young
authors: Zoe
authors: Z
authors: Fonseca-Kelly
authors: Abdolmohamad
authors: A
authors: Rostami
authors: Bruno
authors: B
authors: Gran
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D050838:Interferon Regulatory Factor-3 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D010703:Phorbol Esters / Q000494:pharmacology; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
chemical_list: D016207:Cytokines; D050838:Interferon Regulatory Factor-3; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010703:Phorbol Esters; C445081:myelin oligodendrocyte glycoprotein (35-55); C008874:phorbol-12,13-diacetate