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Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation

Lookup NU author(s): Professor Claire Harris

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 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.


Publication metadata

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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