IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease
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| Publication Date: | 2021 |
| Other Authors: | , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Download full: | http://hdl.handle.net/10451/49649 |
Summary: | © 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
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IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s diseaseAlzheimer’s diseaseIL-17HippocampusMemoryγδ T cells© 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Neuroinflammation in patients with Alzheimer's disease (AD) and related mouse models has been recognized for decades, but the contribution of the recently described meningeal immune population to AD pathogenesis remains to be addressed. Here, using the 3xTg-AD model, we report an accumulation of interleukin-17 (IL-17)-producing cells, mostly γδ T cells, in the brain and the meninges of female, but not male, mice, concomitant with the onset of cognitive decline. Critically, IL-17 neutralization into the ventricles is sufficient to prevent short-term memory and synaptic plasticity deficits at early stages of disease. These effects precede blood-brain barrier disruption and amyloid-beta or tau pathology, implying an early involvement of IL-17 in AD pathology. When IL-17 is neutralized at later stages of disease, the onset of short-memory deficits and amyloidosis-related splenomegaly is delayed. Altogether, our data support the idea that cognition relies on a finely regulated balance of "inflammatory" cytokines derived from the meningeal immune system.This work was funded by the Fundação para a Ciência e Tecnologia (IF/00013/2014, LISBOA-01-0145-FEDER-028241, and PTDC/MED-IMU/1988/2020) to J.C.R., Santa Casa da Misericórdia (MB-7-2018) and Fundacão para a Ciência e Tecnologia (PTDC/BIM-MEC/4778/2014 and IF/00105/2012) to L.V.L., and PD/BD/114103/2015 to H.C.B. The ORCIDs for this article are as follows: 0000-0001-8367-3005 (L.V.L.) and 0000-0002-7852-343X (J.C.R.).ElsevierRepositório da Universidade de LisboaCristiano Brigas, Maria HelenaRibeiro, MiguelCoelho, Joana EGomes, RuiGomez-Murcia, VictoriaCarvalho, KevinFaivre, EmilieCosta Pereira, SaraDarrigues, Juliede Almeida, Afonso AntunesBuée, LucDunot, JadeMarie, HélènePousinha, Paula A.Blum, DavidSilva-Santos, BrunoLopes, Luisa V.Ribot, Julie2021-09-27T14:51:17Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/49649engCell Rep. 2021 Aug 31;36(9):1095742211-124710.1016/j.celrep.2021.109574info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:53:36Zoai:repositorio.ul.pt:10451/49649Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:01:17.376390Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease |
| title |
IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease |
| spellingShingle |
IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease Cristiano Brigas, Maria Helena Alzheimer’s disease IL-17 Hippocampus Memory γδ T cells |
| title_short |
IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease |
| title_full |
IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease |
| title_fullStr |
IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease |
| title_full_unstemmed |
IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease |
| title_sort |
IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease |
| author |
Cristiano Brigas, Maria Helena |
| author_facet |
Cristiano Brigas, Maria Helena Ribeiro, Miguel Coelho, Joana E Gomes, Rui Gomez-Murcia, Victoria Carvalho, Kevin Faivre, Emilie Costa Pereira, Sara Darrigues, Julie de Almeida, Afonso Antunes Buée, Luc Dunot, Jade Marie, Hélène Pousinha, Paula A. Blum, David Silva-Santos, Bruno Lopes, Luisa V. Ribot, Julie |
| author_role |
author |
| author2 |
Ribeiro, Miguel Coelho, Joana E Gomes, Rui Gomez-Murcia, Victoria Carvalho, Kevin Faivre, Emilie Costa Pereira, Sara Darrigues, Julie de Almeida, Afonso Antunes Buée, Luc Dunot, Jade Marie, Hélène Pousinha, Paula A. Blum, David Silva-Santos, Bruno Lopes, Luisa V. Ribot, Julie |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Cristiano Brigas, Maria Helena Ribeiro, Miguel Coelho, Joana E Gomes, Rui Gomez-Murcia, Victoria Carvalho, Kevin Faivre, Emilie Costa Pereira, Sara Darrigues, Julie de Almeida, Afonso Antunes Buée, Luc Dunot, Jade Marie, Hélène Pousinha, Paula A. Blum, David Silva-Santos, Bruno Lopes, Luisa V. Ribot, Julie |
| dc.subject.por.fl_str_mv |
Alzheimer’s disease IL-17 Hippocampus Memory γδ T cells |
| topic |
Alzheimer’s disease IL-17 Hippocampus Memory γδ T cells |
| description |
© 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-09-27T14:51:17Z 2021 2021-01-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/49649 |
| url |
http://hdl.handle.net/10451/49649 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
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Cell Rep. 2021 Aug 31;36(9):109574 2211-1247 10.1016/j.celrep.2021.109574 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Elsevier |
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Elsevier |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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