Frontiers in Immunology | VOL. 13
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Single-cell RNA sequencing of CSF reveals neuroprotective RAC1+ NK cells in Parkinson’s disease

Publication Date Sep 21, 2022

Abstract

Brain infiltration of the natural killer (NK) cells has been observed in several neurodegenerative disorders, including Parkinson’s disease (PD). In a mouse model of α-synucleinopathy, it has been shown that NK cells help in clearing α-synuclein (α-syn) aggregates. This study aimed to investigate the molecular mechanisms underlying the brain infiltration of NK cells in PD. Immunofluorescence assay was performed using the anti-NKp46 antibody to detect NK cells in the brain of PD model mice. Next, we analyzed the publicly available single-cell RNA sequencing (scRNA-seq) data (GSE141578) of the cerebrospinal fluid (CSF) from patients with PD to characterize the CSF immune landscape in PD. Results showed that NK cells infiltrate the substantia nigra (SN) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice and colocalize with dopaminergic neurons and α-syn. Moreover, the ratio of NK cells was found to be increased in the CSF of PD patients. Analysis of the scRNA-seq data revealed that Rac family small GTPase 1 (RAC1) was the most significantly upregulated gene in NK cells from PD patients. Furthermore, genes involved in regulating SN development were enriched in RAC1+ NK cells and these cells showed increased brain infiltration in MPTP-induced PD mice. In conclusion, NK cells actively home to the SN of PD model mice and RAC1 might be involved in regulating this process. Moreover, RAC1+ NK cells play a neuroprotective role in PD.

Concepts

Natural Killer Cells Rac Family Small GTPase 1 Parkinson’s Disease Ratio Of Natural Killer Cells Cerebrospinal Fluid Substantia Nigra Brain Infiltration Single-cell RNA Sequencing scRNA-seq Data Parkinson’s Disease Patients

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No potential conflict of interest was reported by the authors. The conception and design of the study, acquisition of data, analysis and interpretatio...

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