Mechanosensing by Peyer's patch stroma regulates lymphocyte migration and mucosal antibody responses.,Nature Immunology

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Mechanosensing by Peyer's patch stroma regulates lymphocyte migration and mucosal antibody responses.
Nature Immunology ( IF 27.7 ) Pub Date : 2019-10-14 , DOI: 10.1038/s41590-019-0505-z
Jonathan E Chang _{1,

2} , Matthew B Buechler ₃ , Elise Gressier ₂ , Shannon J Turley ₃ , Michael C Carroll _{1,

4}

Affiliation

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.

中文翻译：

Peyer 斑块基质的机械传感调节淋巴细胞迁移和粘膜抗体反应。

成纤维细胞网状细胞 (FRC) 及其被称为“导管”的特殊胶原纤维形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小分子从传入淋巴管输送到淋巴结实质。然而，导管功能的免疫学贡献仍然难以捉摸。在这里，我们报告肠道派尔氏斑 (PPs) 包含一个专门的导管系统，该系统引导吸收的水流过肠道上皮细胞。值得注意的是，PP FRC 通过机械敏感离子通道 Piezo1 对导管流体流动作出反应。表达 CCL19 的基质上的流体流动中断或 Piezo1 的遗传缺陷导致血管周围 FRC 和相关的高内皮小静脉的深刻结构改变。这反过来又损害了淋巴细胞进入 PPs 和黏膜抗体反应的启动。这些结果确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。

更新日期：2019-10-14

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