Fluid absorption modulates Peyer’s patch homeostasis and mucosal antibody responses

Abstract

Abstract Peyer’s patches (PPs) are B cell-rich lymphoid tissues situated throughout the small intestine which play an important role in mucosal antibody responses. PP architecture and stromal cell composition closely resemble that of peripheral lymph nodes despite geographical and functional differences. Notably, fibroblastic reticular cells (FRCs) located in small intestinal PPs form a network of collagen-rich reticular fibers similar to conduits found in lymph nodes. In the PP, these conduits extend from the basement membrane of the epithelial cell lining into the PP follicle, and terminate along blood and efferent lymphatic vessels. Unlike lymph nodes, PPs lack a conventional source of afferent lymph that would normally contribute fluid flow through the conduit network. Instead fluid flow through PP conduits depends largely on water absorbed across the intestinal epithelium. We find that by disrupting water absorption, we can limit or prevent the contribution of absorbed lumenal fluids to the flow of PP conduits. Disruption of fluid absorption subsequently has profound effects on the structural integrity of the high endothelial venule (HEV) and surrounding perivascular FRCs. These alterations correlate with a striking defect in the recruitment of naïve lymphocytes to the PP. Prolonged blockade of water absorption additionally impacts mucosal antibody responses. Antigen-specific fecal IgA titers are reduced, and germinal center responses are decreased in scale. These findings reveal a critical role for fluid absorption and conduit-mediated fluid flow in the maintenance of PP function and may have important implications for mucosal health under conditions of fluid malabsorption, long-term laxative use, and diarrhoeal diseases.