Central nervous system-targeted expression of the complement inhibitor sCrry prevents experimental allergic encephalomyelitis.
Although generally thought of as a T cell-driven autoimmune disease, recent studies in experimental allergic encephalomyelitis (EAE), the animal model of multiple sclerosis, suggest a significant role for innate immune mechanisms. To address the possibility that the complement system plays a central role in these diseases, we developed a transgenic mouse with astrocyte-targeted production of a soluble inhibitor of complement activation, complement receptor-related protein y (sCrry). Here, we show that sCrry transgenic mice are either fully protected against EAE or develop significantly delayed clinical signs. These results indicate that complement activation may have an essential role in the pathogenesis of the disease and that complement-mediated events may occur early during the effector phase of EAE. Furthermore, this work underscores the importance of humoral immunity in amplifying a T cell-initiated pathogenic process.
Davoust
N
N
Department of Microbiology, University of Alabama, Birmingham 35294, USA.
Nataf
S
S
Reiman
R
R
Holers
M V
MV
Campbell
I L
IL
Barnum
S R
SR
D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D003181:Complement C4 / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000276:immunology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D011401:Promoter Regions, Genetic / Q000276:immunology; D011951:Receptors, Complement / Q000096:biosynthesis* / Q000235:genetics; D017463:Receptors, Complement 3b
D003181:Complement C4; C081470:Cr1l protein, mouse; D018076:DNA, Complementary; D005904:Glial Fibrillary Acidic Protein; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011951:Receptors, Complement; D017463:Receptors, Complement 3b