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Central Nervous System-Targeted Expression of the Complement Inhibitor sCrry Prevents Experimental Allergic Encephalomyelitis¹

Nathalie Davoust^*, Serge Nataf^*, Rachael Reiman^*, Michael V. Holers, Iain L. Campbell and Scott R. Barnum^2,*

^* Department of Microbiology, University of Alabama, Birmingham, AL 35294; University of Colorado Health Sciences Center, Denver, CO, 80262; and Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037

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.

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