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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Autores principales:	Yanjun Lu, Ke Li, Yu Hu, Xiong Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Alzheimer’s disease immune infiltration NK cells single-cell sequencing immunity related genes Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/ca91abd13fdf4547a3edb1173c35e588
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spelling	oai:doaj.org-article:ca91abd13fdf4547a3edb1173c35e5882021-11-05T12:43:05ZExpression of Immune Related Genes and Possible Regulatory Mechanisms in Alzheimer’s Disease1664-322410.3389/fimmu.2021.768966https://doaj.org/article/ca91abd13fdf4547a3edb1173c35e5882021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.768966/fullhttps://doaj.org/toc/1664-3224Immune 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.Yanjun LuKe LiYu HuXiong WangFrontiers Media S.A.articleAlzheimer’s diseaseimmune infiltrationNK cellssingle-cell sequencingimmunity related genesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease immune infiltration NK cells single-cell sequencing immunity related genes Immunologic diseases. Allergy RC581-607
spellingShingle	Alzheimer’s disease immune infiltration NK cells single-cell sequencing immunity related genes Immunologic diseases. Allergy RC581-607 Yanjun Lu Ke Li Yu Hu Xiong Wang Expression of Immune Related Genes and Possible Regulatory Mechanisms in Alzheimer’s Disease
description	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.
format	article
author	Yanjun Lu Ke Li Yu Hu Xiong Wang
author_facet	Yanjun Lu Ke Li Yu Hu Xiong Wang
author_sort	Yanjun Lu
title	Expression of Immune Related Genes and Possible Regulatory Mechanisms in Alzheimer’s Disease
title_short	Expression of Immune Related Genes and Possible Regulatory Mechanisms in Alzheimer’s Disease
title_full	Expression of Immune Related Genes and Possible Regulatory Mechanisms in Alzheimer’s Disease
title_fullStr	Expression of Immune Related Genes and Possible Regulatory Mechanisms in Alzheimer’s Disease
title_full_unstemmed	Expression of Immune Related Genes and Possible Regulatory Mechanisms in Alzheimer’s Disease
title_sort	expression of immune related genes and possible regulatory mechanisms in alzheimer’s disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ca91abd13fdf4547a3edb1173c35e588
work_keys_str_mv	AT yanjunlu expressionofimmunerelatedgenesandpossibleregulatorymechanismsinalzheimersdisease AT keli expressionofimmunerelatedgenesandpossibleregulatorymechanismsinalzheimersdisease AT yuhu expressionofimmunerelatedgenesandpossibleregulatorymechanismsinalzheimersdisease AT xiongwang expressionofimmunerelatedgenesandpossibleregulatorymechanismsinalzheimersdisease
_version_	1718444255264899072

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

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