机构:[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China,神经科系统神经内科首都医科大学宣武医院[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China,[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China,[4]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China,[5]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China
The peripheral immune system is thought to affect the pathology of the central nervous system in Alzheimer's disease (AD). However, current knowledge is inadequate for understanding the characteristics of peripheral immune cells in AD. This study aimed to explore the molecular basis of peripheral immune cells and the features of adaptive immune repertoire at a single cell level. We profiled 36,849 peripheral blood mononuclear cells from AD patients with amyloid-positive status and normal controls with amyloid-negative status by 5' single-cell transcriptome and immune repertoire sequencing using the cell ranger standard analysis procedure. We revealed five immune cell subsets: CD4+ T cells, CD8+ T cells, B cells, natural killer cells, and monocytes-macrophages cells, and disentangled the characteristic alterations of cell subset proportion and gene expression patterns in AD. Thirty-one cell type-specific key genes, comprising abundant human leukocyte antigen genes, and multiple immune-related pathways were identified by protein-protein interaction network and pathway enrichment analysis. We also found high-frequency amplification clonotypes in T and B cells and decreased diversity in T cells in AD. As clone amplification suggested the activation of an adaptive immune response against specific antigens, we speculated that the peripheral adaptive immune response, especially mediated by T cells, may have a role in the pathogenesis of AD. This finding may also contribute to further research regarding disease mechanism and the development of immune-related biomarkers or therapy.
基金:
This study was supported by the Key Project of the National Natural
Science Foundation ofChina (81530036); the National Key Scientific
Instrument and Equipment Development Project (31627803); the
Key Project of the National Natural Science Foundation of China
(U20A20354); Beijing Scholars Program; Beijing Brain Initiative
from Beijing Municipal Science & Technology Commission
(Z201100005520016, Z201100005520017).
第一作者机构:[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China,
通讯作者:
通讯机构:[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China,[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China,[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China,[4]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China,[5]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China
推荐引用方式(GB/T 7714):
Hui Xu,Jianping Jia.Single-Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer's Disease[J].FRONTIERS IN IMMUNOLOGY.2021,12:doi:10.3389/fimmu.2021.645666.
APA:
Hui Xu&Jianping Jia.(2021).Single-Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer's Disease.FRONTIERS IN IMMUNOLOGY,12,
MLA:
Hui Xu,et al."Single-Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer's Disease".FRONTIERS IN IMMUNOLOGY 12.(2021)