Alzheimer’s disease alters the transcriptomic profile of natural killer cells at single-cell resolution

Alzheimer’s disease (AD) is the most common dementia without an effective cure at least partially due to incomplete understanding of the disease. Inflammation has emerged as a central player in the onset and progression of AD. As innate lymphoid cells, natural killer (NK) cells orchestrate the initi...

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Vydáno v:Frontiers in immunology Ročník 13; s. 1004885
Hlavní autoři: Qi, Caiyun, Liu, Fang, Zhang, Wenjun, Han, Yali, Zhang, Nan, Liu, Qiang, Li, Handong
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland Frontiers Media S.A 02.11.2022
Témata:
Alzheimer Disease - genetics
Alzheimer’s disease
CD56 Antigen - analysis
CD56 Antigen - genetics
cytotoxicity
Humans
Immunity, Innate
Immunology
innate immunity
Killer Cells, Natural
natural killer cell
single cell sequencing
Transcriptome
single cell sequencing
Alzheimer’s disease
innate immunity
natural killer cell
cytotoxicity
ISSN:1664-3224, 1664-3224
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Shrnutí:Alzheimer’s disease (AD) is the most common dementia without an effective cure at least partially due to incomplete understanding of the disease. Inflammation has emerged as a central player in the onset and progression of AD. As innate lymphoid cells, natural killer (NK) cells orchestrate the initiation and evolution of inflammatory responses. Yet, the transcriptomic features of NK cells in AD remain poorly understood. We assessed the diversity of NK cells using web-based single-cell RNA sequencing data of blood NK cells from patients with AD and control subjects and flow cytometry. We identified a contraction of NK cell compartment in AD, accompanied by a reduction of cytotoxicity. Unbiased clustering revealed four subsets of NK cells in AD, i.e., CD56 bright NK cells, CD56 dim effector NK cells, adaptive NK cells, and a unique NK cell subset that is expanded and characterized by upregulation of CX3CR1, TBX21, MYOM2, DUSP1, and ZFP36L2, and negatively correlated with cognitive function in AD patients. Pseudo-temporal analysis revealed that this unique NK cell subset was at a late stage of NK cell development and enriched with transcription factors TBX21, NFATC2, and SMAD3. Together, our study identified a distinct NK cell subset and its potential involvement in AD.
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Edited by: Lan Wu, Vanderbilt University Medical Center, United States
This article was submitted to NK and Innate Lymphoid Cell Biology, a section of the journal Frontiers in Immunology
Reviewed by: Anil Shanker, Meharry Medical College, United States; Seokmann Hong, Sejong University, South Korea; Lindsay Celada, Baylor College of Medicine, United States
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.1004885