학술논문
CXCR6 orchestrates brain CD8+T cell residency and limits mouse Alzheimer’s disease pathology
Document Type
Article
Author
Su, Wei; Saravia, Jordy; Risch, Isabel; Rankin, Sherri; Guy, Cliff; Chapman, Nicole M.; Shi, Hao; Sun, Yu; KC, Anil; Li, Wei; Huang, Hongling; Lim, Seon Ah; Hu, Haoran; Wang, Yan; Liu, Danting; Jiao, Yun; Chen, Ping-Chung; Soliman, Hadeer; Yan, Koon-Kiu; Zhang, Jonathan; Vogel, Peter; Liu, Xueyan; Serrano, Geidy E.; Beach, Thomas G.; Yu, Jiyang; Peng, Junmin; Chi, Hongbo
Source
Nature Immunology; 20230101, Issue: Preprints p1-13, 13p
Subject
Language
ISSN
15292908; 15292916
Abstract
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, Cxcr6deficiency impairs accumulation, tissue residency programming and clonal expansion of brain PD-1+CD8+T cells. Ablation of Cxcr6or 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.