Dendritic cells are also abundant in the wall of the small intestine outside Peyer’s patches, mainly in the lamina propria. These sample antigens from the lumen and surrounding tissue, and they spend a relatively short time in the intestine before migrating in afferent lymph to the draining mesenteric lymph node, where they present antigen to naive T cells. As elsewhere, migration of dendritic cells depends on the chemokine receptor CCR7 (see Fig. 9.17). It is estimated that 5–10% of the mucosal dendritic cell population emigrates to the mesenteric lymph nodes every day in the resting intestine, allowing constant delivery of antigens from the intestinal surface to T cells. In the absence of infection or inflammation, the encounter between migrating dendritic cells and naive T cells in mesenteric lymph nodes results in the generation of antigen-specific FoxP3+ regulatory T cells that express the gut-homing molecules CCR9 and integrin α4:β7 described above (see Section 12-4). These ‘primed’ Treg cells then leave the lymph node, return to the wall of the small intestine, and suppress the production of inflammatory responses to harmless antigens in food.
Fig. 12.10 Capture of antigens from the intestinal lumen by mononuclear cells in the lamina propria. Top row, first panel: soluble antigens such as food proteins can be transported directly across or between enterocytes, or taken up by M cells in the surface epithelium outside Peyer’s patches. Second panel: enterocytes can capture and internalize antigen:antibody complexes by means of the neonatal Fc receptor (FcRn) on their surface and transport them across the epithelium by transcytosis. Lamina propria dendritic cells express FcRn and other Fc receptors and capture and internalize the complexes. Third panel: an enterocyte infected with an intracellular pathogen undergoes apoptosis and is phagocytosed by a dendritic cell. Lower rows, left panels: mononuclear cells can extend cellular processes between the cells of the epithelium without disturbing its integrity. These cells, now thought to be macrophages, may internalize antigen and pass it to neighboring dendritic cells for presentation to T cells. The micrograph shows mononuclear cells stained for CD11c (green) in the lamina propria of a villus of mouse small intestine. The epithelium appears black but its luminal (outer) surface is shown by the white line. A cell process stretches between two epithelial cells and extends its tip into the lumen of the intestine. Magnification ×200. Center panels: mucus‑secreting goblet cells can transport soluble antigens to lamina propria dendritic cells. The micrograph shows the soluble marker dextran (purple) being transported across goblet cells (white in the bottom right panel) in the epithelium (nuclei stained blue) to underlying dendritic cells (stained for CD11c in green). Scale bar 10 μm. Right panels: dendritic cells (purple) may enter the epithelial layer and capture bacteria before returning to the lamina propria. Dendritic cells and macrophages remaining in the lamina propria are stained blue or green. Scale bar 10 μm. Bottom left, micrograph from Niess, J.H., et al.: Science 2005, 307:254–258. Bottom center, micrograph from McDole, J.R., et al.: Nature 2012, 483:345–349. Bottom right, micrograph from Farache et al.: Immunity 2013, 38:581–595.