Skip to Main content Skip to Navigation
Journal articles

Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation

Bertrand Calippe 1 Sébastien Augustin 1 Fanny Beguier 1 Hugo Charles-Messance 1 Lucie Poupel 2, 3 Jean-Baptiste Conart 1 Shulong Hu 1 Sophie Lavalette 1 Alexandre Fauvet 1 Julie Rayes 4 Olivier Levy 1 William Raoul 1 Catherine Fitting 5 Thomas Denèfle 6, 3, 7 Matthew Pickering 8 Claire Harris 9 Sylvie Jorieux 10 Patrick Sullivan 11 José-Alain Sahel 1 Philippe Karoyan 6, 3, 7 Przemyslaw Sapieha 12 Xavier Guillonneau 1 Emmanuel Gautier 2, 3 Florian Sennlaub 1, *
* Corresponding author
1 Institut de la Vision
2 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition
3 Sorbonne Université
4 CRC (UMR_S 872) - Centre de Recherche des Cordeliers
5 Cytokines et Inflammation
6 LBM UMR 7203 - Laboratoire des biomolécules
7 FR 2769 - Chimie Moléculaire de Paris Centre
8 Department of Medicine - Centre for Complement and Inflammation Research [London, UK]
9 Institute of Infection & Immunity [Cardiff, UK]
10 Laboratoire Français du fractionnement et des Biotechnologies [Lille]
11 Centers for Aging and Geriatric Research Education and Clinical Center - Department of Medicine [Durham, NC, USA]
12 Department of Ophthalmology [Montreal, QC, Canada]
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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [42 references]  Display  Hide  Download
https://www.hal.inserm.fr/inserm-01755551
Contributor : William Raoul <>
Submitted on : Friday, March 30, 2018 - 4:36:23 PM
Last modification on : Thursday, February 18, 2021 - 10:42:07 AM

Files

Vignette du document
2017text Immunity (1).pdf
Files produced by the author(s)

Identifiers

Collections

INSERM | PASTEUR | CNRS | UPMC | ENS-PARIS | ICAN | CORDELIERS | LBM | U968 | USPC | UNIV-PARIS5 | LBM-E1 | MICHEM | SORBONNE-UNIVERSITE | ENSCP | INC-CNRS | PARISTECH | SU-MEDECINE | SU-SCIENCES | UNIV-PARIS | ESPCI-PSL | PSL | ESPCI | SU-TI

Citation

Bertrand Calippe, Sébastien Augustin, Fanny Beguier, Hugo Charles-Messance, Lucie Poupel, et al.. Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation. Immunity, Elsevier, 2017, 46 (2), pp.261 - 272. ⟨10.1016/j.immuni.2017.01.006⟩. ⟨inserm-01755551⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

979

Files downloads

1467