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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / metabolism
  • Cell Movement / immunology
  • Chemokine CCL19 / metabolism
  • Female
  • Immunity, Mucosal*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Intestine, Small / immunology
  • Intestine, Small / metabolism
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Lymphocyte Activation
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Male
  • Mechanotransduction, Cellular / immunology*
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Peyer's Patches / immunology*
  • Peyer's Patches / metabolism
  • Water / metabolism

Substances

  • Antibodies
  • Ccl19 protein, mouse
  • Chemokine CCL19
  • Ion Channels
  • Piezo1 protein, mouse
  • Water