CXCR6 orchestrates brain CD8+ T cell residency and limits mouse Alzheimer's disease pathology

NATURE IMMUNOLOGY(2023)

引用 8|浏览24
暂无评分
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 beta-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.
更多
查看译文
关键词
mouse alzheimers,alzheimers disease,cell
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要