Goblet cell-associated antigen passages and luminal antigen delivery to intestinal dendritic cells (71.6)

Abstract

Abstract Understanding how pathogen-specific immunity is elicited in the gut against the overwhelming background of foreign antigens from food and normal flora is essential for treating intestinal infections and inflammatory diseases. Oral tolerance is mediated in part by intestinal dendritic cells (DCs) that promote the development of regulatory T cells. Beneath the villous epithelium, the lamina propria (LP) contains a large population of DCs (CD11c+ CD11b+ MHCII+ cells), CD103+ CX3CR1- DCs, which can promote IgA production, imprint gut homing on lymphocytes, and induce the development of regulatory T cells, and CD103- CX3CR1+ DCs, which can contribute to TNFα production, colitis, and the development of Th17 T cells. How luminal antigens are captured by LP-DCs in the steady-state is controversial. Using a combination of in vivo two-photon imaging and ex vivo analyses we show that goblet cells (GCs) within the small intestine function as passages to deliver low-molecular weight antigens from the intestinal lumen to underlying CD103+ LP-DCs, a phenomenon we have termed goblet-cell associated antigen passages (GAPs). The preferential delivery of antigens to CD103+ LP-DCs has important implications for peripheral tolerance induction at the mucosa. The mechanisms that regulate GAP function during homeostasis and pathogenic infection are the focus of ongoing work.