黄斑变性
中性粒细胞胞外陷阱
NKG2D公司
脉络膜新生血管
细胞毒性T细胞
细胞生物学
自然杀伤细胞
人口
癌症研究
趋化因子
炎症
免疫学
生物
医学
眼科
环境卫生
体外
生物化学
作者
Xue Dong,Yinting Song,Y. Liu,Xuejing Kou,Tian-Jing Yang,Samuel Shi,Kai He,Yiming Li,Ziqi Li,Xueming Yao,Ju Guo,Bohao Cui,Ziru Wu,Yi Lei,Xiaohong Wang,Mei Chen,Heping Xu,Qiang Liu,Fu‐Dong Shi,Xiaohong Wang,Hua Yan
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2024-08-14
卷期号:16 (760)
标识
DOI:10.1126/scitranslmed.adi6626
摘要
Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions in patients with nvAMD and in mouse models. Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex–mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD.
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