Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy

Autor: Cécile Delarasse, Yuan Dong, Yann Monnet, Raphaëlle Caillierez, Susanna Schraen-Maschke, Luc Buée, Antoine Leboucher, Sylvie Burnouf, Nadège Zommer, Cyril Laurent, François-Pierre Légeron, Elodie Martin, Guillaume Dorothée, Stéphane Hunot, Nathalie Jouy, Dominique Demeyer, Kevin Carvalho, Emilie Faivre, Véronique Sazdovitch, David Blum, Marie Duchamp
Přispěvatelé: Blum, David, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Unité de Virologie clinique et fondamentale (UVCF), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, STMicroelectronics [Rousset] (ST-ROUSSET), Physico-Chimie-Curie (PCC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Système immunitaire et neuroinflammation [CRSA], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
CD3 Complex
T cells
Hippocampus
Mice
Transgenic
chemokines
CD8-Positive T-Lymphocytes
Hippocampal formation
Antibodies
neuroinflammation
Mice
03 medical and health sciences
0302 clinical medicine
mental disorders
medicine
Animals
Humans
Dementia
Cognitive Dysfunction
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Cognitive decline
Neuroinflammation
ComputingMilieux_MISCELLANEOUS
Aged
Cerebral Cortex
Inflammation
tauopathy
Original Articles
Frontotemporal lobar degeneration
Middle Aged
medicine.disease
Pathophysiology
Mice
Inbred C57BL
Disease Models
Animal
frontotemporal lobar degeneration
030104 developmental biology
Tauopathies
Immunology
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Neurology (clinical)
Tauopathy
Psychology
Neuroscience
030217 neurology & neurosurgery
Zdroj: Brain-A Journal of Neurology
Brain-A Journal of Neurology, 2016, 140 (1), pp.184-200. ⟨10.1093/brain/aww270⟩
Brain-A Journal of Neurology, Oxford University Press (OUP), 2016, 140 (1), pp.184-200. ⟨10.1093/brain/aww270⟩
Brain-A Journal of Neurology, 2017, 140 (1), pp.184-200. ⟨10.1093/brain/aww270⟩
Brain
ISSN: 0006-8950
1460-2156
Popis: The role of immune responses in the cognitive impairments associated with tauopathy is unclear. Laurent et al. identify a CD8+ T-cell infiltration in the hippocampus of THY-Tau22 transgenic mice. T-cell depletion reverses spatial memory deficits in these animals, supporting a role for hippocampal T-cell infiltration in tau-driven cognitive impairments.
Alzheimer’s disease is characterized by the combined presence of amyloid plaques and tau pathology, the latter being correlated with the progression of clinical symptoms. Neuroinflammatory changes are thought to be major contributors to Alzheimer’s disease pathophysiology, even if their precise role still remains largely debated. Notably, to what extent immune responses contribute to cognitive impairments promoted by tau pathology remains poorly understood. To address this question, we took advantage of the THY-Tau22 mouse model that progressively develops hippocampal tau pathology paralleling cognitive deficits and reappraised the interrelationship between tau pathology and brain immune responses. In addition to conventional astroglial and microglial responses, we identified a CD8-positive T cell infiltration in the hippocampus of tau transgenic mice associated with an early chemokine response, notably involving CCL3. Interestingly, CD8-positive lymphocyte infiltration was also observed in the cortex of patients exhibiting frontemporal dementia with P301L tau mutation. To gain insights into the functional involvement of T cell infiltration in the pathophysiological development of tauopathy in THY-Tau22 mice, we chronically depleted T cells using anti-CD3 antibody. Such anti-CD3 treatment prevented hippocampal T cell infiltration in tau transgenic animals and reverted spatial memory deficits, in absence of tau pathology modulation. Altogether, these data support an instrumental role of hippocampal T cell infiltration in tau-driven pathophysiology and cognitive impairments in Alzheimer’s disease and other tauopathies.
Databáze: OpenAIRE
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