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
Description: 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 B-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.
Subject headings: CD8+ T cells; CXCR6; Alzheimer’s disease; Neurodegenerative diseases; Inflammation; Brain
Publication year: 2023
Journal or book title: Nature Immunology
Volume: 24
Issue: 10
Pages: 1735-1747
Find the full text: https://www.nature.com/articles/s41590-023-01604-z
Find more like this one (cited by): https://scholar.google.com/scholar?cites=3867953232241605020&as_sdt=1000005&sciodt=0,16&hl=en
Serial number: 3868