Central nervous system expression of interferon regulatory factor 1 regulates experimental autoimmune encephalomyelitis.
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.
Ren
Zhihua
Z
Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center, 1725 W. Harrison Street, Suite 309, Chicago, IL 60612, USA.
Wang
Yan
Y
Tao
Duan
D
Liebenson
David
D
Liggett
Thomas
T
Goswami
Rajendra
R
Stefoski
Dusan
D
Balabanov
Roumen
R
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D050856:Interferon Regulatory Factor-1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D050856:Interferon Regulatory Factor-1