The P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's disease mouse model.
CCL8
MHCII
PLCG2
T cells
chimeric Alzheimer's mouse model
human leukocyte antigen
human stem cell-derived microglia
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
29
11
2021
received:
23
03
2021
accepted:
30
11
2021
pubmed:
11
2
2022
medline:
21
10
2022
entrez:
10
2
2022
Statut:
ppublish
Résumé
The P522R variant of PLCG2, expressed by microglia, is associated with reduced risk of Alzheimer's disease (AD). Yet, the impact of this protective mutation on microglial responses to AD pathology remains unknown. Chimeric AD and wild-type mice were generated by transplanting PLCG2-P522R or isogenic wild-type human induced pluripotent stem cell microglia. At 7 months of age, single-cell and bulk RNA sequencing, and histological analyses were performed. The PLCG2-P522R variant induced a significant increase in microglial human leukocyte antigen (HLA) expression and the induction of antigen presentation, chemokine signaling, and T cell proliferation pathways. Examination of immune-intact AD mice further demonstrated that the PLCG2-P522R variant promotes the recruitment of CD8
Identifiants
pubmed: 35142046
doi: 10.1002/alz.12577
pmc: PMC9360195
mid: NIHMS1765930
doi:
Substances chimiques
Amyloid beta-Peptides
0
Chemokines
0
PLCG2 protein, human
EC 3.1.4.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1765-1778Subventions
Organisme : NIA NIH HHS
ID : R01 AG056303
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG074566
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066519
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016573
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061895
Pays : United States
Organisme : NIDA NIH HHS
ID : RF1 DA048813
Pays : United States
Organisme : NIA NIH HHS
ID : U54 AG054345
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG048099
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS014609
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG055524
Pays : United States
Informations de copyright
© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
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