Goblet cells deliver luminal retinoids and imprint CD103+ lamina propria dendritic cells (P3223)

Abstract

Abstract The intestinal lamina propria (LP) underlies the villous epithelia and contains a large population of CD103+ myeloid DCs. CD103+ LP-DCs generate the vitamin A metabolite all-trans retinoic acid (ATRA) and promote intestinal type responses including generating Foxp3+ T regulatory cells, imprinting gut homing expression on lymphocytes, and facilitating IgA production. In vivo studies demonstrated that luminal retinoids from the diet or bile are required to condition intestinal LP-DCs to generate ATRA. How luminal retinoids confer this capacity is not known. Goblet cell associated antigen passages (GAPs) provides a portal for CD103+ LP-DCs to acquire soluble luminal substances and goblet cell (GCs) proteins, suggesting a role for GCs and GAPs in imprinting CD103+ LP-DCs. Using an in vivo two-photon (2P) imaging approach, we found that GAPs delivered luminal retinoids and the enzyme required to metabolize pro-vitamin A to LP-DCs. In the absence of GCs, LP-DCs are not imprinted with ALDH activity. We observed that LP-DCs express CCR6, which was required for LP-DCs to associate with the small intestine epithelium. CCR6 deficient LP-DCs do not acquire GC proteins or luminal antigens, do not become imprinted with ALDH activity, and are impaired at inducing ATRA dependent events. These findings demonstrate that GAPs deliver luminal retinoids and the enzymes required to metabolize these retinoids to CD103+ LP-DCs, and accordingly play a critical role in imprinting CD103+ LP-DCs.