Protection from autoimmune brain inflammation in mice lacking IFN‐regulatory factor‐1 is associated with Th2‐type cytokines

T Buch, C Uthoff‐Hachenberg… - International …, 2003 - academic.oup.com
T Buch, C Uthoff‐Hachenberg, A Waisman
International immunology, 2003academic.oup.com
Abstract 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 …
Abstract
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 Th2‐type and decreased production of Th1‐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 Th2.
Oxford University Press