Cellular & Molecular Immunology
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2025
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IF 19.8
Bai Ying,Ren Hui,Leng Shuo,Yuan Mengqin,Jiang YiXin,Zhang Shenyang,Wang Yu,Ju Minzi,Wang Zhi,Xi Wen,Xu Lian,Zheng Bingjing,Li Daxing,Huo Xinchen,Zhu Tianhao,Zhang Beicheng,Shen Ling,Zhang Yuan,Jiang Wei,Zhang John H.,Han Bing,Yao Honghong
Splenic sympathetic activity critically modulates peripheral immunity after ischemic stroke, thus intervention in spleen sympathetic activity represents a promising therapeutic strategy for stroke. However, the mechanisms underlying spleen-brain-immune axis communication remain poorly understood. Here, we utilized a surgical denervation protocol to perform splenic sympathetic denervation (SDN), which significantly attenuated brain injury following stroke. Through single-cell RNA sequencing, we identified a novel GZMK + CD8 + CD27 + CCR7 + T-cell subset in patients with acute ischemic stroke (AIS), which we designated stroke-associated T (Tsa) cells. The expansion of Tsa cells was positively correlated with the severity of clinical symptoms and was driven by the splenic sympathetic nervous system. Stroke-induced sympathetic activation triggers the release of splenic norepinephrine (NE), which preferentially signals through ADRB2 on Tsa cells to promote their mobilization. Additionally, ischemic injury induces endothelial cell-specific expression of CCL19, which chemoattracts Tsa cells into the brain parenchyma via their cognate CCR7 receptor, exacerbating neuroinflammatory injury and neurological deficits in a transient middle cerebral artery occlusion (tMCAO) mouse model. We developed a CCR7-targeting peptide to disrupt this chemotactic axis and reduce T-cell infiltration, thereby mitigating brain injury. Our findings highlight SDN as a promising therapeutic strategy to attenuate ischemia‒reperfusion injury and suggest its potential as an adjunctive therapy for reperfusion treatment in AIS patients.
研究领域:
神经科学
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免疫学
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卒中研究
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神经免疫学
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分子生物学
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细胞生物学
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生物医学研究
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药理学
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系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Yong Wang,Chaoyu Pu,Zeyu Han,Yawei Du,Liang Chen,Yanran Huang,Yue Luo,Chao Xiang,Jiangtao He,Lu Chen,Wenguo Cui,Ke Jiang,Yuling Li
Efferocytosis in macrophages typically engages an anti-inflammatory positive feedback regulatory mechanism. In osteoarthritis (OA), characterized by imbalanced inflammatory homeostasis, the proinflammatory state of macrophages in the immune microenvironment can be reversed through enhanced efferocytosis. This study develops an in situ proefferocytosis hydrogel microsphere (macrophage polarity converter, H-C@IL) for OA treatment. Immunoliposomes (IL), CD16/32 antibody-modified clodronate liposomes, are initially prepared using the Re-emulsion method. Then, the IL is loaded into CCL19-modified HAMA microspheres through microfluidic technology. In vitro, H-C@IL can specifically recruit M0 and M1 macrophages via CCL19, induce apoptosis in M1 macrophages through secondary targeting with IL, and provide “Find/Eat-me” signals to enhance in situ efferocytosis. Additionally, it promotes macrophage polarization toward the M2 phenotype. In vivo, behavioral, imaging, and histological analyses demonstrate that H-C@IL effectively facilitates macrophage polarization toward M2, inhibits inflammation, and promotes cartilage regeneration. Mechanistically, H-C@IL enhances efferocytosis by activating proteins such as PROS1 and TIMD4 in M0 macrophages. Concurrently, signaling pathways, including PQLC2-Arg-Rac1 and Pbx1/IL-10, are activated to drive the polarization of macrophages from M0 to M2. In summary, H-C@IL promotes M0 macrophage efferocytosis in situ, facilitates macrophage polarization toward M2, restores inflammatory homeostasis, and promotes cartilage regeneration, offering a comprehensive treatment strategy for OA.
研究领域:
生物医学工程
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免疫学
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骨科
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）