Subcapsular sinus macrophage sensing of extracellular matrix rigidity alters membrane topography and immune complex mobility
Subcapsular sinus macrophage sensing of extracellular matrix rigidity alters membrane topography and immune complex mobility
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被膜下窦巨噬细胞对细胞外基质刚性的感知改变了膜形貌和免疫复合物的迁移性
DOI：
10.1101/2022.12.02.518873
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Iliopoulou M
中科院分区：
文献类型：
--
作者：
Iliopoulou M
被膜下窦巨噬细胞（SSMs）通过形成免疫屏障控制病原体从淋巴到淋巴结滤泡的运输，在免疫防御中发挥关键作用。SSM通过将抗原直接呈递给幼稚B细胞和通过向滤泡树突细胞提供抗原以传播生发中心反应来参与抗体应答。尽管SSM在免疫反应中发挥着重要作用，但对其细胞生物学知之甚少，因为它们在体外分离和研究方面具有技术挑战性。在这里，我们使用多色荧光显微镜来识别培养中的淋巴结来源的SSM。我们专注于SSM作为抗原呈递细胞的作用，发现它们的肌动蛋白细胞骨架调节细胞表面上显示的免疫复合物的空间组织和流动性。此外，我们确定SSM是机械敏感细胞，其通过改变肌动蛋白细胞骨架的结构来响应细胞外基质（ECM）刚性的变化，从而导致细胞形态、膜形貌和免疫复合物流动性的变化。我们的研究结果揭示了一种新的机制，调节抗原呈递细胞的抗原呈递的物理方面，这可能对B细胞活化和抗体应答有影响。
Subcapsular sinus macrophages (SSMs) play a key role in immune defence by forming immunological barriers that control the transport of pathogens from lymph into lymph node follicles. SSMs participate in antibody responses by presenting antigens directly to naive B cells and by supplying antigens to follicular dendritic cells to propagate germinal centre reactions. Despite the prominent roles that SSMs play during immune responses, little is known about their cell biology because they are technically challenging to isolate and studyin vitro. Here, we used multi-colour fluorescence microscopy to identify lymph nodederived SSMs in culture. We focused on the role of SSMs as antigen-presenting cells and found that their actin cytoskeleton regulates the spatial organisation and mobility of immune complexes displayed on the cell surface. Moreover, we determined that SSMs are mechanosensitive cells that respond to changes in extracellular matrix (ECM) rigidity by altering the architecture of the actin cytoskeleton, leading to changes in cell morphology, membrane topography, and immune complex mobility. Our results reveal a new mechanism regulating physical aspects of antigen presentation by antigen-presenting cells, which may have implications for B cell activation and antibody responses.
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影响因子：
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作者：
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