Expression of Immune Related Genes and Possible Regulatory Mechanisms in Alzheimer’s Disease

Immune infiltration of peripheral natural killer (NK) cells in the brain has been observed in Alzheimer’s disease (AD). Immunity-related genes (IRGs) play an essential role in immune infiltration; however, the expression of IRGs and possible regulatory mechanisms involved in AD remain unclear. The p...

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Vydáno v:Frontiers in immunology Ročník 12; s. 768966
Hlavní autoři: Lu, Yanjun, Li, Ke, Hu, Yu, Wang, Xiong
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland Frontiers Media S.A 05.11.2021
Témata:
Alzheimer Disease - blood
Alzheimer Disease - genetics
Alzheimer’s disease
Brain - metabolism
Brain - pathology
Cells, Cultured
Cluster Analysis
Databases, Genetic
Gene Ontology
Gene Regulatory Networks
Humans
immune infiltration
Immunity - genetics
immunity related genes
Immunology
Killer Cells, Natural - cytology
Killer Cells, Natural - metabolism
Leukocytes, Mononuclear - metabolism
NK cells
RNA-Seq - methods
Single-Cell Analysis - methods
single-cell sequencing
Transcription Factors - genetics
Transcriptome - genetics
single-cell sequencing
NK cells
immunity related genes
Alzheimer’s disease
immune infiltration
ISSN:1664-3224, 1664-3224
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Shrnutí:Immune infiltration of peripheral natural killer (NK) cells in the brain has been observed in Alzheimer’s disease (AD). Immunity-related genes (IRGs) play an essential role in immune infiltration; however, the expression of IRGs and possible regulatory mechanisms involved in AD remain unclear. The peripheral blood mononuclear cells (PBMCs) single-cell RNA (scRNA) sequencing data from patients with AD were analyzed and PBMCs obtained from the ImmPort database were screened for cluster marker genes. IRG activity was calculated using the AUCell package. A bulk sequencing dataset of AD brain tissues was analyzed to explore common IRGs between PBMCs and the brain. Relevant regulatory transcription factors (TFs) were identified from the Human TFDB database. The protein-protein interaction network of key TFs were generated using the STRING database. Eight clusters were identified, including memory CD4 T, NKT, NK, B, DC, CD8 T cells, and platelets. NK cells were significantly decreased in patients with AD, while CD4 T cells were increased. NK and DC cells exhibited the highest IRG activity. GO and KEGG analyses of the scRNA and bulk sequencing data showed that the DEGs focused on the immune response. Seventy common IRGs were found in both peripheral NK cells and the brain. Seventeen TFs were associated with IRG expression, and the PPI network indicated that STAT3, IRF1, and REL were the hub TFs. In conclusion, we propose that peripheral NK cells may infiltrate the brain and contribute to neuroinflammatory changes in AD through bioinformatic analysis of scRNA and bulk sequencing data. Moreover, STAT3 may be involved in the transcriptional regulation of IRGs in NK cells.
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Edited by: Liwu Li, Virginia Tech, United States
Reviewed by: John R Lukens, University of Virginia, United States; Huw Lewis, GlaxoSmithKline, United Kingdom
This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology
These authors have contributed equally to this work
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.768966