A Gut Feeling Special immune controls are necessary in the gut to prevent the immune system from reacting to the commensal microbiota and to food antigens. Dendritic cells (DCs) are important for maintaining gut tolerance because they help to keep T cells in an unresponsive state. However, in other environments, DCs activate T cells. What signals determine whether DCs induce T cell tolerance or activation? Manicassamy et al. (p. 849 ; see the Perspective by Mellman and Clausen ) found that β-catenin–dependent signaling is required for maintaining DC-mediated gut tolerance in mice. Wnt ligands were expressed in the gut, and β-catenin signaling was activated in DCs in the small and large intestines but not in the spleen. When β-catenin was specifically deleted from DCs in mice, the frequency of regulatory T cells and anti-inflammatory cytokines was reduced, whereas the frequency of pro-inflammatory T helper 1 and T helper 17 cells and their associated cytokines was increased. Mice lacking β-catenin in dendritic cells also exhibited enhanced susceptibility in a mouse model of colitis.

Activation of β-Catenin in Dendritic Cells Regulates Immunity Versus Tolerance in the Intestine