Dendritic cells (DCs) and macrophages are critical to innate and adaptive immunity to the intestinal bacterial microbiota. Here, we identify a myeloid-derived mucosal DC in mice, which populates the entire lamina propria of the small intestine. Lamina propria DCs were found to depend on the chemokine receptor CX3CR1 to form transepithelial dendrites, which enable the cells to directly sample luminal antigens. CX3CR1 was also found to control the clearance of entero-invasive pathogens by DCs. Thus, CX3CR1-dependent processes, which control host interactions of specialized DCs with commensal and pathogenic bacteria, may regulate immunological tolerance and inflammation.

T cell activation by dendritic cells (DCs) is critical to the initiation of adaptive immune responses and protection against pathogens. Here, we demonstrate that a specialized DC subset in Peyer's patches (PPs) mediates the rapid activation of pathogen specific T cells. This DC subset is characterized by the expression of the chemokine receptor CCR6 and is found only in PPs. CCR6(+) DCs were recruited into the dome regions of PPs upon invasion of the follicle associated epithelium (FAE) by an enteric pathogen and were responsible for the rapid local activation of pathogen-specific T cells. CCR6-deficient DCs were unable to respond to bacterial invasion of PPs and failed to initiate T cell activation, resulting in reduced defense against oral infection. Thus, CCR6-dependent regulation of DCs is responsible for localized T cell dependent defense against entero-invasive pathogens.

Claudin-2 is a structural component of tight junctions in the kidneys, liver, and intestine, but the mechanisms regulating its expression have not been defined. The 5-flanking region of the claudin-2 gene contains binding sites for intestine-specific Cdx homeodomain proteins and hepatocyte nuclear factor (HNF)-1, which are conserved in human and mouse. Both Cdx1 and Cdx2 activated the claudin-2 promoter in the human intestinal epithelial cell line Caco-2. HNF-1␣ augmented the Cdx2-induced but not Cdx1-induced transcriptional activation of the human claudin-2 promoter. In mice, HNF-1␣ was required for claudin-2 expression in the villus epithelium of the ileum and within the liver but not in the kidneys, indicating an organ-specific function of HNF-1␣ in the regulation of claudin-2 gene expression. Tight junction structural components, which determine epithelial polarization and intestinal barrier function, can be regulated by homeodomain proteins that control the differentiation of the intestinal epithelium.