Format

Send to

Choose Destination
Nat Immunol. 2019 Nov;20(11):1506-1516. doi: 10.1038/s41590-019-0505-z. Epub 2019 Oct 14.

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

Author information

1
Division of Medical Sciences, Harvard Medical School, Boston, MA, USA.
2
Program in Cellular and Molecular Medicine, Children's Hospital, Boston, MA, USA.
3
Department of Cancer Immunology, Genentech, South San Francisco, CA, USA.
4
Department of Cancer Immunology, Genentech, South San Francisco, CA, USA. turley.shannon@gene.com.
5
Division of Medical Sciences, Harvard Medical School, Boston, MA, USA. michael.carroll@childrens.harvard.edu.
6
Department of Pediatrics, Harvard Medical School, Boston, MA, USA. michael.carroll@childrens.harvard.edu.

Abstract

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.

PMID:
31611698
DOI:
10.1038/s41590-019-0505-z

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center