Left: CX3CR1⁺ DCs extend protrusions across the epithelial barrier. These cells also express CD70 and drive the differentiation of Th17 cells via a mechanism dependent on ATP and/or flagellin. CD103⁺ DCs migrate into the draining MLN, where they promote the conversion of Foxp3⁺ Tregs via an RA- and TGF-β–dependent mechanism. Tregs also upregulate the expression of the gut-homing marker α₄β₇. A third population of APCs of non–bone marrow origin expressing CD70⁺ is required for T cell proliferation directly in the LP. Right: The phenotype of CD103⁺ LP DCs is conferred by the local microenvironment, in particular by IECs via the release of TGF-β, RA, and — in the human system — TSLP. CD103⁺ DCs acquire the ability to drive the differentiation of Tregs and to inhibit Th1 and Th17 cell development. Macrophages also limit intestinal inflammation via activation of Tregs and inhibition of the ability of CX3CR1⁺ DCs to drive Th17 cell development. Macrophages retain full antibactericidal activity.