{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318014/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318014"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"CX3CL1 (fractalkine)-CX3CR1 Interface Drives CD8⁺ T Cell-Induced Neurodegeneration in Human Brain Organoids","description":"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.","dates":{"publication":"2026/09/18"},"accession":"GSE318014","cross_references":{"GSM":["GSM9484519","GSM9484529","GSM9484526","GSM9484525","GSM9484528","GSM9484527","GSM9484521","GSM9484524","GSM9484523","GSM9484531","GSM9484530"],"GPL":["20301"],"GSE":["318014"],"taxon":["Homo sapiens"]}}