Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation - PubMed (original) (raw)

. 2017 Feb 21;46(2):261-272.

doi: 10.1016/j.immuni.2017.01.006.

Sebastien Augustin 1, Fanny Beguier 1, Hugo Charles-Messance 1, Lucie Poupel 2, Jean-Baptiste Conart 1, Shulong J Hu 1, Sophie Lavalette 1, Alexandre Fauvet 1, Julie Rayes 3, Olivier Levy 1, William Raoul 1, Catherine Fitting 4, Thomas Denèfle 5, Matthew C Pickering 6, Claire Harris 7, Sylvie Jorieux 8, Patrick M Sullivan 9, José-Alain Sahel 1, Philippe Karoyan 5, Przemyslaw Sapieha 10, Xavier Guillonneau 1, Emmanuel L Gautier 2, Florian Sennlaub 11

Affiliations

• PMID: 28228282
• DOI: 10.1016/j.immuni.2017.01.006

Free article

Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation

Bertrand Calippe et al. Immunity. 2017.

Free article

Abstract

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.

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Comment in

• Compliments of Factor H: What's in it for AMD?
  Mattapallil MJ, Caspi RR. Mattapallil MJ, et al. Immunity. 2017 Feb 21;46(2):167-169. doi: 10.1016/j.immuni.2017.02.008. Immunity. 2017. PMID: 28228273 Free PMC article.

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