先天免疫系统
炎症
骨髓
免疫系统
造血
潮湿
下调和上调
冲程(发动机)
免疫学
单核细胞
免疫
小胶质细胞
生物
中风恢复
医学
祖细胞
干细胞
癌症研究
神经科学
细胞生物学
气象学
工程类
康复
物理
基因
机械工程
生物化学
作者
Tze‐Yen Lin,Danye Jiang,W. Chen,Jhih Syuan Lin,X. Zhang,Chih‐Hung Chen,Chia‐Lang Hsu,Liang‐Chuan Lai,Ping‐Hung Chen,Kai‐Chien Yang,Lauren Sansing,C. Chang
标识
DOI:10.15252/embr.202357164
摘要
Abstract A high‐salt diet (HSD) elicits sustained sterile inflammation and worsens tissue injury. However, how this occurs after stroke, a leading cause of morbidity and mortality, remains unknown. Here, we report that HSD impairs long‐term brain recovery after intracerebral hemorrhage, a severe form of stroke, despite salt withdrawal prior to the injury. Mechanistically, HSD induces innate immune priming and training in hematopoietic stem and progenitor cells (HSPCs) by downregulation of NR4a family and mitochondrial oxidative phosphorylation. This training compromises alternative activation of monocyte‐derived macrophages (MDMs) without altering the initial inflammatory responses of the stroke brain. Healthy mice transplanted with bone marrow from HSD‐fed mice retain signatures of reduced MDM reparative functions, further confirming a persistent form of innate immune memory that originates in the bone marrow. Loss of NR4a1 in macrophages recapitulates HSD‐induced negative impacts on stroke outcomes while gain of NR4a1 enables stroke recovery in HSD animals. Together, we provide the first evidence that links HSD‐induced innate immune memory to the acquisition of persistent dysregulated inflammatory responses and unveils NR4a1 as a potential therapeutic target.
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