CXCR6 orchestrates brain CD8+ T cell residency and limits murine Alzheimer’s disease pathology. Nature Immunology
发布时间：2025-10-10
点击次数：
- 发表刊物：
- Nature Immunology
- 摘要：
- Neurodegenerative diseases, including Alzheimer’s disease (AD), are characterized by innate immune-mediated inflammation, but functional and mechanistic effects of the adaptive immune system remain unclear. Here we identify brain-resident CD8+ T cells that coexpress CXCR6 and PD-1 and are in proximity to plaque-associated microglia in human and mouse AD brains. We also establish that CD8+ T cells restrict AD pathologies, including β-amyloid deposition and cognitive decline. Ligand–receptor interaction analysis identifies CXCL16–CXCR6 intercellular communication between microglia and CD8+ T cells. Further, Cxcr6 deficiency impairs accumulation, tissue residency programming and clonal expansion of brain PD-1+CD8+ T cells. Ablation of Cxcr6 or CD8+ T cells ultimately increases proinflammatory cytokine production from microglia, with CXCR6 orchestrating brain CD8+ T cell–microglia colocalization. Collectively, our study reveals protective roles for brain CD8+ T cells and CXCR6 in mouse AD pathogenesis and highlights that microenvironment-specific, intercellular communication orchestrates tissue homeostasis and protection from neuroinflammation.
- 论文类型：
- 期刊论文
- 是否译文：
- 否
- 发表时间：
- 2023-09-07