Core Insights - The research identifies a new macrophage subpopulation, CX3CR1 and CD63 double-positive macrophages, that plays a crucial role in maintaining liver immune homeostasis [1][2][3] - The study utilizes advanced imaging techniques to analyze the spatial arrangement and molecular phenotype of macrophages in the liver, revealing their unique transcriptional characteristics [2] - The findings suggest that this macrophage subpopulation is not only vital for immune regulation but also provides neuroprotection, indicating its potential as a therapeutic target for liver-related diseases [2][3] Group 1 - The study was conducted by researchers from Hainan University, focusing on the liver's unique immune cell composition and the role of macrophages in immune homeostasis [1] - The liver is described as a unique immune organ composed of various immune cells, with macrophages being essential for maintaining immune balance [1][2] - The research highlights the significance of the liver portal area, where dysfunction is linked to various liver diseases, yet the immune cell subpopulations and their mechanisms remain poorly understood [1] Group 2 - The researchers employed the Liver-CUBIC optical clearing imaging technology to achieve single-cell resolution imaging of the liver [2] - The study found that the liver portal area macrophage subpopulation plays a key role in immune homeostasis and neuroprotection by interacting with T cells and sympathetic nerves [2] - In a non-alcoholic steatohepatitis mouse model, the absence of this macrophage subpopulation led to increased neutrophil infiltration and aggravated sympathetic nerve damage, underscoring its importance [2] Group 3 - The research provides new insights into the spatial heterogeneity of liver portal area macrophages, contributing to the fields of liver immunology and neuroimmunology [3] - The findings may lead to the development of more effective macrophage-targeted therapies aimed at restoring tissue integrity or treating organ-specific diseases [3] - The accompanying commentary in Nature Immunology emphasizes the strategic positioning of these macrophage subpopulations in maintaining organ integrity [3]

Core Viewpoint - The study reveals that maternal immune activation due to viral infection leads to abnormal secretion of extracellular granzyme B (GzmB) by natural killer (NK) cells, which crosses the maternal-fetal barrier, resulting in the accumulation of fetal macrophages and activation of microglia, ultimately causing neurodevelopmental disorders and behavioral defects in offspring [2][3][6]. Group 1: Research Findings - Maternal NK cells activated by viral infection promote the accumulation of activated macrophages in the fetal brain, leading to neurodevelopmental disorders and behavioral defects in offspring [3][6]. - Extracellular granzyme B (GzmB) is released by maternal CD49a+ tissue-resident NK cell subsets under type I interferon stimulation, crossing the maternal-fetal barrier and promoting the accumulation of fetal macrophages expressing interferon-stimulated genes (ISG) and activation of microglia [3][6]. - Targeting extracellular GzmB by systemic administration of serine protease inhibitor Serpina3n or knocking out the GzmB gene in maternal NK cells can alleviate neuroimmune disorders in the fetal brain induced by maternal immune activation [3][6]. Group 2: Implications - The findings indicate that exposure to a disrupted maternal environment reprograms the immune function of decidual NK cells, disrupting the neuroimmune balance in the fetus and increasing the risk of neurodevelopmental disorders in offspring [6].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 动脉粥样硬化 （ Atherosclerosis， AS） 已被证实是 血管性认知障碍 （VCI） 的一个独立危险因素，但其机制尚不明确。 2025 年 5 月 8 日，华中科技大学同济医学院附属同济医院 秦川 教授、 田代实 教授、 王伟 教授等在 Cell 子刊 Cell Metabolism 上发表了题为： The foam cell-derived exosomes exacerbate ischemic white matter injury via transmitting metabolic defects to microglia 的研究论文。 该研究发现， 动脉粥样硬化 斑块中 巨噬细胞来源的泡沫细胞 产生的 外泌体 ，可传递氧化还原失衡和代谢缺陷至中枢神经系统中的 小胶质细胞 ，从而加剧 缺 血性白质损伤 和 血管性认知障碍 。 这项研究揭示了外周巨噬细胞与大脑内小胶质细胞之间存在远距离联系，为动脉粥样硬化诱导的血管性认知障碍提供了新见解和潜在治疗靶点。 在这项最新研究中，研究团队发现， 动脉粥样硬化 （ AS） 患者循环系统中的 外泌体 （exos ...