IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease

Autor: Sara Costa-Pereira, Jade Dunot, David Blum, Bruno Silva-Santos, Emilie Faivre, Luísa V. Lopes, Julie C. Ribot, Joana E. Coelho, Hélène Marie, Paula A. Pousinha, Rui Gomes, Miguel Ribeiro, Julie Darrigues, Afonso Antunes de Almeida, Victoria Gomez-Murcia, Luc Buée, Helena C. Brigas, Kevin Carvalho
Přispěvatelé: Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Universidade de Lisboa (ULISBOA), Excellence Laboratory LabEx DISTALZ, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Universidade de Lisboa = University of Lisbon (ULISBOA), Lille Neurosciences & Cognition - U 1172 (LilNCog), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Repositório da Universidade de Lisboa, BUEE, Luc
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Mice
129 Strain
hippocampus
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Anti-Inflammatory Agents
Hippocampus
Mice
Transgenic
Disease
γδ T cells
General Biochemistry
Genetics and Molecular Biology
memory
03 medical and health sciences
Cognition
0302 clinical medicine
Memory
Alzheimer Disease
Animals
Medicine
Intraepithelial Lymphocytes
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
0303 health sciences
Neuronal Plasticity
Behavior
Animal
business.industry
Interleukin-17
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Antibodies
Monoclonal
Brain
Antibodies
Neutralizing
3. Good health
Disease Models
Animal
IL-17
Memory
Short-Term
Neuroinflammatory Diseases
Synapses
Female
Interleukin 17
Inflammation Mediators
business
Alzheimer’s disease
Neuroscience
030217 neurology & neurosurgery
Zdroj: Cell Reports
Cell Reports, Elsevier Inc, 2021, 36 (9), pp.109574. ⟨10.1016/j.celrep.2021.109574⟩
Cell Reports, 2021, 36 (9), pp.109574. ⟨10.1016/j.celrep.2021.109574⟩
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2021.109574⟩
Popis: © 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.).
Databáze: OpenAIRE
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