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Mechanosensing by Peyer's patch stroma regulates lymphocyte migration and mucosal antibody responses

机译:Peyer的蛋白质基质机械溶解调节淋巴细胞迁移和粘膜抗体反应

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摘要

Fibroblastic reticular cells (FRCs) and their specialized collagen fibers termed 'conduits' form fundamental structural units supporting lymphoid tissues. In lymph nodes, conduits are known to transport interstitial fluid and small molecules from afferent lymphatics into the nodal parenchyma. However, the immunological contributions of conduit function have remained elusive. Here, we report that intestinal Peyer's patches (PPs) contain a specialized conduit system that directs the flow of water absorbed across the intestinal epithelium. Notably, PP FRCs responded to conduit fluid flow via the mechanosensitive ion channel Piezo1. Disruption of fluid flow or genetic deficiency of Piezo1 on CCL19-expressing stroma led to profound structural alterations in perivascular FRCs and associated high endothelial venules. This in turn impaired lymphocyte entry into PPs and initiation of mucosal antibody responses. These results identify a critical role for conduit-mediated fluid flow in the maintenance of PP homeostasis and mucosal immunity.
机译:肌纤维咬合细胞(FRCS)及其专用胶原纤维称为“导管”构成支持淋巴组织的基本结构单元。在淋巴结中,已知导管将间质液和来自传入淋巴管的小分子运送到节点实质中。然而,导管函数的免疫学贡献仍然难以捉摸。在这里,我们报告说,肠道Peyer的贴片(PPS)包含一个专门的导管系统,指示肠上皮吸收的水流。值得注意的是,PP FRCS通过机械敏感离子通道压电1响应导管流体流动。 CCL19表达基质CCL19表达基质中的流体流动或压电遗传缺乏的破坏导致血管外患者和相关的高内皮静脉中的深刻结构改变。这反过来是淋巴细胞进入pps和粘膜抗体反应的启动。这些结果鉴定了导管介导的流体流动在维持PP稳态和粘膜免疫中的关键作用。

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