Central nervous system expression of interferon regulatory factor 1 regulates experimental autoimmune encephalomyelitis.

ABSTRACT

Interferon regulatory factor 1 (IRF-1) is a transcription factor that has been implicated in the disease mechanisms of experimental autoimmune encephalomyelitis (EAE). In this study, we examined the role of central nervous system (CNS) expression of IRF-1 in the natural course of EAE. In an effort to dissect the CNS effects from the peripheral immune effects of IRF-1, we generated bone marrow chimera mice that differentially expressed IRF-1 in the CNS and in the immune system. We found that mice lacking IRF-1 in the CNS developed significantly milder clinical symptoms and shorter disease duration compared to those with wild-type background. Based on these results, we concluded that the CNS expression of IRF-1 regulates the disease process in EAE. Our findings are relevant to the inflammatory mechanisms involved in multiple sclerosis and may provide a basis for development of novel therapeutic targets of the disease.