{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China",
    "State 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",
    "School 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."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shushan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhanghong Luo"
    },
    {
      "affs": [
        1
      ],
      "name": "Yishuai Tan"
    },
    {
      "affs": [
        0
      ],
      "name": "Bo Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Xiao"
    },
    {
      "affs": [
        0
      ],
      "name": "Guohui Jiang"
    },
    {
      "affs": [
        2
      ],
      "name": "Tao Zhu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0y5d3bf48a1d0.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bbrep.2026.102861",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2405580826004218",
  "id": "0y5d3bf48a1d0",
  "issns": [
    "2405-5808"
  ],
  "landing_url": "https://doi.org/10.1016/j.bbrep.2026.102861",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QD415-436"
    ],
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "openalex",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W7225157619",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/0y5d3bf48a1d0.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T14:21:20Z",
      "native_id": "059b517a3f4e49879be9fb29dab968bc",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.bbrep.2026.102861"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Neuroinflammation and Neurodegeneration Mechanisms",
      "subfield": "neurology"
    }
  ],
  "title": "Multi-omics profiling suggests deep brain stimulation-associated expansion of CLIC3+ NK cells attenuates neuroinflammation in Parkinson's disease",
  "title_text": "Multi-omics profiling suggests deep brain stimulation-associated expansion of CLIC3+ NK cells attenuates neuroinflammation in Parkinson's disease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T14:21:20Z",
  "url": "https://research.draconitic.com/paper/0y5d3bf48a1d0",
  "venue": "Biochemistry and Biophysics Reports",
  "versions": []
}