{
  "abstract": "Immune–neuron interactions play a critical role in neuroinflammatory and neurodegenerative diseases, such as Alzheimer’s disease (AD), but how CD8⁺ T cells contribute to brain pathology remains poorly understood. Amyloid-β (Aβ), a hallmark of AD, is known to trigger neuronal stress and inflammation. Here, we established a human cortical organoid (hCO) model to investigate CD8⁺ T cell responses to Aβ-induced neurodegenerative stress. Aβ exposure increased neuronal expression of CX3CL1 (fractalkine), which engages its receptor CX3CR1 on CD8⁺ T cells. Transwell migration assays showed enhanced recruitment of CX3CR1⁺ CD8⁺ T cells toward Aβ-treated hCOs. In parallel, Aβ upregulated IL-15 expression, a cytokine that supports CD8⁺ T cell activation. The infiltration of CD8⁺ T cells led to neuronal injury, marked by MAP2 loss and cleaved Caspase-3 activation, accompanied by an increase in gene signatures for cell death and inflammation. Exposure to the conditioned medium of activated CX3CR1high CD8⁺ T cell recapitulated this damage, and the neutralization of CD8+ T cell cytokines and cytotoxic molecules rescued the phenotype. These findings identify the CX3CL1–CX3CR1 axis and CD8⁺ T cell effector programs as drivers of neurotoxicity and establish brain organoids as a platform to study immune-driven neurodegeneration.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Genetics, Interdepartmental Neuroscience Program, Yale Stem Cell Center, Yale Child Study Center, Wu Tsai Institute, Yale School of Medicine, New Haven, CT 06520",
    "Department of Internal Medicine, Section of Rheumatology, Allergy & Immunology, Yale School of Medicine, New Haven, CT 06520",
    "College of Pharmacy, Sookmyung Women’s University, Seoul 04310, Republic of Korea",
    "Department of Pathology, Yale School of Medicine, New Haven, CT 06520"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Woo Sub Yang",
      "orcid": "0000-0002-2358-8287"
    },
    {
      "affs": [
        1
      ],
      "name": "Min Sun Shin",
      "orcid": "0000-0003-2516-9251"
    },
    {
      "affs": [
        0
      ],
      "name": "Mu Seog Choe"
    },
    {
      "affs": [
        0
      ],
      "name": "Ferdi Ridvan Kiral"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jumee Kim"
    },
    {
      "affs": [
        1
      ],
      "name": "Hong-Jai Park",
      "orcid": "0000-0003-0659-5896"
    },
    {
      "affs": [
        1
      ],
      "name": "Mario Felix",
      "orcid": "0009-0003-8586-8326"
    },
    {
      "affs": [
        1
      ],
      "name": "Lais Osmani",
      "orcid": "0000-0001-7131-390X"
    },
    {
      "affs": [
        0
      ],
      "name": "In-Hyun Park",
      "orcid": "0000-0001-7748-1293"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Insoo Kang",
      "orcid": "0000-0001-7483-1171"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0c52vqsjdjdhg.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2605209123",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13715762/",
  "id": "0c52vqsjdjdhg",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://doi.org/10.1073/pnas.2605209123",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "424"
    ],
    [
      "heading",
      "Biological Sciences"
    ],
    [
      "heading",
      "Neuroscience"
    ],
    [
      "openalex",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W7223028306",
  "pdf_url": null,
  "pmcid": "PMC13715762",
  "pmid": "42900735",
  "published": "2026-10-20",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/0c52vqsjdjdhg.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:58Z",
      "native_id": "PMC13715762",
      "source": "pmc",
      "url": "https://doi.org/10.1073/pnas.2605209123"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "CX3CL1 (fractalkine)–CX3CR1 interface drives CD8⁺ T cell–induced neurodegeneration in human brain organoids",
  "title_text": "CX3CL1 (fractalkine)–CX3CR1 interface drives CD8⁺ T cell–induced neurodegeneration in human brain organoids",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:58Z",
  "url": "https://research.draconitic.com/paper/0c52vqsjdjdhg",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}