Localization of dendritic cells in the gut epithelium requires MAdCAM-1.

ABSTRACT

Directed migration of immune cells is a prerequisite for immune responses. T and B cell migration to the gut is secured by interaction of mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) and ß7 integrin. Here we report a novel function for MAdCAM-1 that of mediating intestinal localization of dendritic cells (DCs). In homeostasis, both MAdCAM-1-deficient and ß7 integrin-deficient mice exhibit a reduced frequency of CD11c(+) cells, including CD103(+) DCs and plasmacytoid DCs (pDCs), in the gut epithelium. Deficiency of either MAdCAM-1 or ß7 integrin reduces the migration efficiency of pDCs into the intestinal intraepithelial (IE) compartment. Both mouse strains display a decreased migration efficiency of precursors for conventional DCs (cDCs), from the circulation into the epithelium. By contrast, the migration of activated DCs from the small intestine to MLN is unchanged in MAdCAM-1-deficient mice. These findings suggest that MAdCAM-1 is important for the ß7 integrin-dependent intestinal localization of both cDCs and pDCs.