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Journal articles
CCR2(+) monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice.
Florian Sennlaub
1, 2, *
Constance Auvynet
1, 3, 4
Bertrand Calippe
1
Sophie Lavalette
1
Lucie Poupel
4
Shulong Hu
1
Elisa Dominguez
1
Serge Camelo
1, 3
Olivier Levy
1
Elodie Guyon
1, 4
Noah Saederup
5, 6
Israel Charo
5, 6
Nico Van Rooijen
7
Emeline Nandrot
1
Jean-Louis Bourges
2, 3
Francine Behar-Cohen
3, 2
José-Alain Sahel
1
Xavier Guillonneau
1
William Raoul
1
Christophe Combadiere
4, 8
*
Corresponding author
Florian Sennlaub 1, 2
Correspondent author
Constance Auvynet 1, 3, 4
Author
Bertrand Calippe 1
Author
Sophie Lavalette 1
Author
Olivier Levy 1
Author
Elodie Guyon 1, 4
Author
Noah Saederup 5, 6
Author
Israel F. Charo 5, 6
Author
Nico Van Rooijen 7
Author
Emeline Nandrot 1
Author IdHAL : emeline-nandrot ResearcherId : http://www.researcherid.com/rid/AAN-3925-2020 ORCID : https://orcid.org/0000-0003-3087-078X
Jean-Louis Bourges 2, 3
Author
Francine Behar-Cohen 3, 2
Author
José-Alain Sahel 1
Author
Xavier Guillonneau 1
Author
William Raoul 1
Author IdHAL : william-raoul
Christophe Combadiere 4, 8
Author IdHAL : christophe-combadiere ResearcherId : http://www.researcherid.com/rid/I-5639-2013 ORCID : https://orcid.org/0000-0002-1755-4531
1
Institut de la Vision (17 Rue Moreau, 75012 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7210 (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U968 (101, rue de Tolbiac, 75013 Paris - France)
- UPMC - Université Pierre et Marie Curie - Paris 6 : UM80 (4 place Jussieu - 75005 Paris - France)
2
Service d'ophtalmologie [Hôtel-Dieu - Paris] (Paris - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- Hôtel-Dieu (France)
3
CRC (UMR_S 872) - Centre de Recherche des Cordeliers (CRBM des Cordeliers 15, rue de l'ecole de medecine batiment E 75270 Paris cedex 06 - France)
- UPD5 - Université Paris Descartes - Paris 5 : U872 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U872 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR 872 (France)
4
Immunité et Infection (France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
- IFR113 (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U945 (101, rue de Tolbiac, 75013 Paris - France)
5
Gladstone Institute of Cardiovascular Disease (San Francisco CA 94158 - United States)
- UCSF - University of California [San Francisco] (505 Parnassus Ave, San Francisco, CA 94143 - United States)
- University of California (United States)
6
Department of Medicine (505 Parnassus Ave San Francisco, CA 94122 - United States)
- UCSF - University of California [San Francisco] (505 Parnassus Ave, San Francisco, CA 94143 - United States)
- University of California (United States)
- Cardiovascular Research Institute (France)
7
Department of Molecular Cell Biology (Amsterdam - Netherlands)
- Free University Medical Center [Amsterdam] (Netherlands)
8
Service d'immunologie [CHU Pitié-Salpétrière] (47-83, boulevard de l'Hôpital 75651 PARIS Cedex 13 - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
- Sorbonne Université (France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
Abstract : Atrophic age-related macular degeneration (AMD) is associated with the subretinal accumulation of mononuclear phagocytes (MPs). Their role in promoting or inhibiting retinal degeneration is unknown. We here show that atrophic AMD is associated with increased intraocular CCL2 levels and subretinal CCR2(+) inflammatory monocyte infiltration in patients. Using age- and light-induced subretinal inflammation and photoreceptor degeneration in Cx3cr1 knockout mice, we show that subretinal Cx3cr1 deficient MPs overexpress CCL2 and that both the genetic deletion of CCL2 or CCR2 and the pharmacological inhibition of CCR2 prevent inflammatory monocyte recruitment, MP accumulation and photoreceptor degeneration in vivo. Our study shows that contrary to CCR2 and CCL2, CX3CR1 is constitutively expressed in the retina where it represses the expression of CCL2 and the recruitment of neurotoxic inflammatory CCR2(+) monocytes. CCL2/CCR2 inhibition might represent a powerful tool for controlling inflammation and neurodegeneration in AMD.
Document type :
Journal articles
Complete list of metadata
https://www.hal.inserm.fr/inserm-00912837
Contributor : William Raoul <>
Submitted on : Monday, December 2, 2013 - 4:54:45 PM
Last modification on : Tuesday, December 22, 2020 - 4:06:02 PM
Long-term archiving on: : Monday, March 3, 2014 - 10:06:14 AM
Contributor : William Raoul <>
Submitted on : Monday, December 2, 2013 - 4:54:45 PM
Last modification on : Tuesday, December 22, 2020 - 4:06:02 PM
Long-term archiving on: : Monday, March 3, 2014 - 10:06:14 AM
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emmm201302692-1.pdf
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Identifiers
- HAL Id : inserm-00912837, version 1
- DOI : 10.1002/emmm.201302692
- PUBMED : 24142887
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INSERM | UNIV-PARIS5 | CNRS | UPMC | U968 | CORDELIERS | USPC | SORBONNE-UNIVERSITE | SU-MEDECINE | SU-SCIENCES | UNIV-PARIS | SU-TI
Citation
Florian Sennlaub, Constance Auvynet, Bertrand Calippe, Sophie Lavalette, Lucie Poupel, et al.. CCR2(+) monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice.. EMBO Molecular Medicine, Wiley Open Access, 2013, 5 (11), pp.1775-93. ⟨10.1002/emmm.201302692⟩. ⟨inserm-00912837⟩
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