Protection from autoimmune brain inflammation in mice lacking IFN-regulatory factor-1 is associated with Th2-type cytokines.
IFN-regulatory factor-1 (IRF-1) is a transcription factor that regulates the expression of IFN-induced genes and type I IFN. It has previously been demonstrated that IRF-1-deficient mice show reduced susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by a peptide from myelin basic protein. To further study the role of IRF-1 in brain inflammation, we analyzed EAE induced by immunization with a myelin oligodendrocyte glycoprotein-derived peptide in 129/Sv mice lacking IRF-1. We found that these mice were almost completely resistant to EAE induction and that this unresponsiveness was intrinsically related to the IRF-1 deficiency of the T cells, but not with any other cell type. Furthermore, we show that the amelioration of EAE was associated with increased production of T(h)2-type and decreased production of T(h)1-type cytokines. These results demonstrate that absence of IRF-1 in myelin-specific T cells results in protection from severe EAE and is associated with a skewing of the T cell response towards T(h)2.
Buch
Thorsten
T
Laboratory of Molecular Immunology, Institute for Genetics, University of Cologne, Weyertal 121, 50931 Cologne, Germany.
Uthoff-Hachenberg
Claudia
C
Waisman
Ari
A
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D050856:Interferon Regulatory Factor-1; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger