Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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; Denèfle, T; Pickering, MC; Harris, C; Jorieux, S; Sullivan, PM; Sahel, J-A; Karoyan, P; Sapieha, P; Guillonneau, X; Gautier, EL; Sennlaub, F

Published Date

  • February 21, 2017

Published In

Volume / Issue

  • 46 / 2

Start / End Page

  • 261 - 272

PubMed ID

  • 28228282

Pubmed Central ID

  • 28228282

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2017.01.006

Language

  • eng

Conference Location

  • United States