CD4 T Cells Induce A Subset of MHCII-Expressing Microglia that Attenuates Alzheimer Pathology.
Biological Sciences
Cell Biology
Immunology
Neuroscience
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
28 Jun 2019
28 Jun 2019
Historique:
received:
18
11
2018
revised:
01
04
2019
accepted:
28
05
2019
pubmed:
17
6
2019
medline:
17
6
2019
entrez:
17
6
2019
Statut:
ppublish
Résumé
Microglia play a key role in innate immunity in Alzheimer disease (AD), but their role as antigen-presenting cells is as yet unclear. Here we found that amyloid β peptide (Aβ)-specific T helper 1 (Aβ-Th1 cells) T cells polarized to secrete interferon-γ and intracerebroventricularly (ICV) injected to the 5XFAD mouse model of AD induced the differentiation of major histocompatibility complex class II (MHCII)+ microglia with distinct morphology and enhanced plaque clearance capacity than MHCII- microglia. Notably, 5XFAD mice lacking MHCII exhibited an enhanced amyloid pathology in the brain along with exacerbated innate inflammation and reduced phagocytic capacity. Using a bone marrow chimera mouse model, we showed that infiltrating macrophages did not differentiate to MHCII+ cells following ICV injection of Aβ-Th1 cells and did not support T cell-mediated amyloid clearance. Overall, we demonstrate that CD4 T cells induce a P2ry12+ MHCII+ subset of microglia, which play a key role in T cell-mediated effector functions that abrogate AD-like pathology.
Identifiants
pubmed: 31203186
pii: S2589-0042(19)30176-2
doi: 10.1016/j.isci.2019.05.039
pmc: PMC6581663
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
298-311Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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