IRF-1 signaling in central nervous system glial cells regulates inflammatory demyelination.
The present study provides evidence that interferon regulatory factor 1 (IRF-1) signaling in glial cells is involved in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Using a bone marrow chimera model of EAE, we demonstrated that CNS IRF-1 regulates inflammatory demyelination and disease severity independently of the peripheral immune cells. In addition, we identified Caspase 1, a pro-inflammatory and pro-apoptotic molecule, as an important transcriptional target of IRF-1. The findings of our study indicate that IRF-1 signaling in glial cells serves as a final common pathway of inflammatory demyelination and may have important clinical implications in MS.
Rush University Medical Center, Department of Neurological Sciences, Multiple Sclerosis Center, 1725 W. Harrison Street, Suite 309, Chicago, IL 60612, United States.
Zhihua
Z
Ren
Yan
Y
Wang
David
D
Liebenson
Thomas
T
Liggett
Rajendra
R
Goswami
Dusan
D
Stefoski
Roumen
R
Balabanov
D000818:Animals; D002478:Cells, Cultured; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects / Q000276:immunology*; D050856:Interferon Regulatory Factor-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D009457:Neuroglia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
D050856:Interferon Regulatory Factor-1