The physiological immune response in the intestine against dietary proteins and commensal flora is characterized by regulatory mechanisms (tolerance) that prevent harmful consequences. Intestinal dendritic cells (DCs) have a central role in the development of immunosuppressive regulatory T cells owing to their ability to produce TGF-β and retinoic acid (RA). However, the article under evaluation shows an unexpected effect of RA - that of promoting a proinflammatory phenotype in intestinal DCs involved in the generation of inflammatory immune responses to dietary antigens. By using a double transgenic murine model that resembles human celiac disease, it was demonstrated that RA synergizes with IL-15 in promoting the breakdown of gluten tolerance and the development of enteropathy. The tissue microenvironment modulates DC function, and immune therapies that are based on RA aiming to restore oral tolerance should be used with caution because the presence of IL-15 (and/or other proinflammatory cytokines) may have undesirable effects.