Multi-omics profiling suggests deep brain stimulation-associated expansion of CLIC3+ NK cells attenuates neuroinflammation in Parkinson's disease
- 1Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
- 2State Key Laboratory of Molecular Oncology & Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China; West China School of Pharmacy, Sichuan University, Chengdu, 610041, Sichuan, China
- 3School of Public Health, North Sichuan Medical College, Nanchong, Sichuan, China; Corresponding author.School of Public Health, North Sichuan Medical CollegeNorth Sichuan Medical College, Nanchong, Sichuan, China.
Abstract
Deep brain stimulation (DBS) alleviates Parkinson's disease (PD) symptoms, but its immunomodulatory mechanisms remain elusive. Through integrating microarray (GSE23676), single cell/nucleus RNA-seq (GSE184950, GSE202210, GSE223138, GSE243639; after quality control (mitochondrial gene content <25%, gene number >200) 616,076 high-quality cells were included), and GWAS data, we identified CLIC3 as a DBS-associated, potential protective implications in PD. CLIC3 was selectively up-regulated in a distinct natural killer cell subset (NK_CLIC3), which secreted TGFB1 to restrain neuroinflammation. CellChat and immunohistochemistry revealed that NK_CLIC3 cells communicated with PD-relevant neuronal populations: excitatory (SLC18A2+), inhibitory (SLC18A2+), oligodendrocyte (SLC18A2+), and astrocytic (SLC18A2+) cells via THY1–ADGRE5 and GZMA–PARD3 axes. Immune infiltration analysis (GSE114517; n = 75) suggested NK infiltration and deficient M2 macrophage recruitment in PD brains, underscoring an inadequate anti-inflammatory response. We further isolated CLIC3-positive NK cells (from a healthy donor) by fluorescence-activated cell sorting (FACS) and confirmed their ability to degrade α-synuclein, the pathological protein in Parkinson's disease, supporting the potential NK(CLIC3+) cells' protective function in PD. Our findings suggest DBS may expand NK_CLIC3 cells to suppress neuroinflammation through TGFB1 mediated immune–neuronal crosstalk, positioning CLIC3 as a prospective therapeutic target for PD.
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BibTeX
@article{zhang2026multiomics,
title = {{Multi-omics profiling suggests deep brain stimulation-associated expansion of CLIC3+ NK cells attenuates neuroinflammation in Parkinson's disease}},
author = {Shushan Zhang and Zhanghong Luo and Yishuai Tan and Bo Cheng and Wei Xiao and Guohui Jiang and Tao Zhu},
journal = {Biochemistry and Biophysics Reports},
year = {2026},
month = nov,
doi = {10.1016/j.bbrep.2026.102861},
url = {https://doi.org/10.1016/j.bbrep.2026.102861},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multi-omics profiling suggests deep brain stimulation-associated expansion of CLIC3+ NK cells attenuates neuroinflammation in Parkinson's disease
AU - Shushan Zhang
AU - Zhanghong Luo
AU - Yishuai Tan
AU - Bo Cheng
AU - Wei Xiao
AU - Guohui Jiang
AU - Tao Zhu
PY - 2026
DA - 2026/11/05
JO - Biochemistry and Biophysics Reports
DO - 10.1016/j.bbrep.2026.102861
UR - https://doi.org/10.1016/j.bbrep.2026.102861
AB - Deep brain stimulation (DBS) alleviates Parkinson's disease (PD) symptoms, but its immunomodulatory mechanisms remain elusive. Through integrating microarray (GSE23676), single cell/nucleus RNA-seq (GSE184950, GSE202210, GSE223138, GSE243639; after quality control (mitochondrial gene content <25%, gene number >200) 616,076 high-quality cells were included), and GWAS data, we identified CLIC3 as a DBS-associated, potential protective implications in PD. CLIC3 was selectively up-regulated in a distinct natural killer cell subset (NK_CLIC3), which secreted TGFB1 to restrain neuroinflammation. CellChat and immunohistochemistry revealed that NK_CLIC3 cells communicated with PD-relevant neuronal populations: excitatory (SLC18A2+), inhibitory (SLC18A2+), oligodendrocyte (SLC18A2+), and astrocytic (SLC18A2+) cells via THY1–ADGRE5 and GZMA–PARD3 axes. Immune infiltration analysis (GSE114517; n = 75) suggested NK infiltration and deficient M2 macrophage recruitment in PD brains, underscoring an inadequate anti-inflammatory response. We further isolated CLIC3-positive NK cells (from a healthy donor) by fluorescence-activated cell sorting (FACS) and confirmed their ability to degrade α-synuclein, the pathological protein in Parkinson's disease, supporting the potential NK(CLIC3+) cells' protective function in PD. Our findings suggest DBS may expand NK_CLIC3 cells to suppress neuroinflammation through TGFB1 mediated immune–neuronal crosstalk, positioning CLIC3 as a prospective therapeutic target for PD.
SN - 2405-5808
ER -