Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation

被引：131

作者：

Calippe, Bertrand ^{[1
]}

Augustin, Sebastien ^{[1
]}

Beguier, Fanny ^{[1
]}

Charles-Messance, Hugo ^{[1
]}

Poupel, Lucie ^{[2
]}

Conart, Jean-Baptiste ^{[1
]}

Hu, Shulong J. ^{[1
]}

Lavalette, Sophie ^{[1
]}

Fauvet, Alexandre ^{[1
]}

Rayes, Julie ^{[3
]}

Levy, Olivier ^{[1
]}

Raoul, William ^{[1
]}

Fitting, Catherine ^{[15
]}

Denefle, Thomas ^{[10
,11
,12
,13
]}

Pickering, Matthew C. ^{[4
]}

Harris, Claire ^{[5
]}

Jorieux, Sylvie ^{[6
]}

Sullivan, Patrick M. ^{[7
,8
,9
]}

Sahel, Jose -Alain ^{[1
]}

Karoyan, Philippe ^{[10
,11
,12
,13
]}

Sapieha, Przemyslaw ^{[14
]}

Guillonneau, Xavier ^{[1
]}

Gautier, Emmanuel L. ^{[2
]}

Sennlaub, Florian ^{[1
]}

机构：

[1] UPMC Univ Paris 06, Sorbonne Univ, Inst Vis, INSERM,CNRS, 17 Rue Moreau, F-75012 Paris, France

[2] UPMC Univ Paris 06, Sorbonne Univ, INSERM, UMR S 1166,Fac Med Pitie Salpetriere, 91 Blvd Hop, F-75013 Paris, France

[3] Univ Paris 05, Unite Mixte Rech Sante 872, Ctr Rech Cordeliers, F-75006 Paris, France

[4] Imperial Coll, Ctr Complement & Inflammat Res, Dept Med, London W12 0NN, England

[5] Cardiff Univ, Inst Infect & Immun, Cardiff CF10 3XQ, S Glam, Wales

[6] LFB Biotechnol, F-59000 Lille, France

[7] Duke Univ, Dept Med, Ctr Aging, Durham, NC 27710 USA

[8] Duke Univ, Dept Med, Ctr Geriatr Res Educ, Durham, NC 27710 USA

[9] Duke Univ, Dept Med, Ctr Clin, Durham Veteran Affairs Med Ctr, Durham, NC 27710 USA

[10] Univ Paris 06, Sorbonne Univ, Lab Biomol, UMR 7203, Paris, France

[11] Univ Paris 06, Sorbonne Univ, FR 2769, Paris, France

[12] CNRS, UMR 7203, Paris, France

[13] Ecole Normale Super, Dept Chim, F-75005 Paris, France

[14] Univ Montreal, Dept Ophthalmol, Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ H3T 1J4, Canada

[15] Inst Pasteur, Dept Infect & Epidemiol, Unite Cytokines & Inflammat, F-75015 Paris, France

来源：

IMMUNITY | 2017年 / 46卷 / 02期

关键词：

MACULAR DEGENERATION; SUBRETINAL INFLAMMATION; GENE-EXPRESSION; UP-REGULATION; SPINAL-CORD; MICROGLIA; DISEASE; MACROPHAGES; ANGIOGENESIS; ACTIVATION;

D O I：

10.1016/j.immuni.2017.01.006

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：261 / 272

页数：12

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