CCR6 expression by small intestine lamina propria dendritic cells is critical for surveillance of the luminal contents at the villous epithelial surface (CCR5P.251)

Abstract

Abstract The immune system underlying the villous epithelium is continually monitoring its complex environment to appropriately respond with the induction of tolerance or immunity. However little is known about the factors promoting immune surveillance of the luminal contents at this surface. Mice deficient in lymphotoxin beta receptor (LTBR) have a decreased population of dendritic cells (DCs) associated with the villous epithelium. The chemokine CCL20 is expressed by the villous epithelium in a LTBR dependent manner, and CCR6, the only receptor for CCL20, is expressed by the LP-DCs associating with the villous epithelium. Using an in vivo imaging approach, we observed that LP-DC from CCR6 deficient mice were further from the intestinal lumen and flow cytometric analysis revealed they had a decreased population of epithelia associated LP-DCs. Mixed bone marrow transfers confirmed that CCR6 expression by DCs was required for association with the epithelium. In vivo imaging and flow cytometry revealed that LP-DCs from CCR6-/- mice were not impaired at migrating in the lymphatics or populating the mesenteric lymph node. However LP-DCs from CCR6-/- mice were deficient at acquiring epithelial cell proteins and intraluminal ovalbumin, and were deficient in priming immune responses to luminal antigen in the mesenteric lymph nodes. These findings identify an essential role for CCR6 expression by LP-DCs in surveillance of the luminal environment at the villous epithelial surface.