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Lookup NU author(s): Professor Claire Harris
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2017 Elsevier Inc. Variants of the CFH gene, encoding complement factor H (CFH), show strong association with age-related macular degeneration (AMD), a major cause of blindness. Here, we used murine models of AMD to examine the contribution of CFH to disease etiology. Cfh deletion protected the mice from the pathogenic subretinal accumulation of mononuclear phagocytes (MP) that characterize AMD and showed accelerated resolution of inflammation. MP persistence arose secondary to binding of CFH to CD11b, which obstructed the homeostatic elimination of MPs from the subretinal space mediated by thrombospsondin-1 (TSP-1) activation of CD47. The AMD-associated CFH(H402) variant markedly increased this inhibitory effect on microglial cells, supporting a causal link to disease etiology. This mechanism is not restricted to the eye, as similar results were observed in a model of acute sterile peritonitis. Pharmacological activation of CD47 accelerated resolution of both subretinal and peritoneal inflammation, with implications for the treatment of chronic inflammatory disease.
Author(s): Calippe B, Augustin S, Beguier F, Charles-Messance H, Poupel L, Conart J-B, Hu SJ, Lavalette S, Fauvet A, Rayes J, Levy O, Raoul W, Fitting C, Denefle T, Pickering MC, Harris C, Jorieux S, Sullivan PM, Sahel J-A, Karoyan P, Sapieha P, Guillonneau X, Gautier EL, Sennlaub F
Publication type: Article
Publication status: Published
Journal: Immunity
Year: 2017
Volume: 46
Issue: 2
Pages: 261-272
Print publication date: 21/02/2017
Online publication date: 24/02/2017
Acceptance date: 12/12/2016
Date deposited: 20/02/2019
ISSN (print): 1074-7613
ISSN (electronic): 1097-4180
Publisher: Cell Press
URL: https://doi.org/10.1016/j.immuni.2017.01.006
DOI: 10.1016/j.immuni.2017.01.006
PubMed id: 28228282
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