Identification of antigen-presenting cell–T cell interactions driving immune responses to food

The intestinal immune system must concomitantly tolerate food and commensals and protect against pathogens. Antigen-presenting cells (APCs) orchestrate these immune responses by presenting luminal antigens to CD4⁺ T cells and inducing their differentiation into regulatory (peripheral regulatory T cell) or inflammatory [T helper (Th) cell] subsets. We used a proximity labeling method (LIPSTIC) to identify APCs that presented dietary antigens under tolerizing and inflammatory conditions and to understand cellular mechanisms by which tolerance to food is induced and can be disrupted by infection. Helminth infections disrupted tolerance induction proportionally to the reduction in the ratio between tolerogenic APCs-including migratory dendritic cells (cDC1s) and Rorγt⁺ APCs-and inflammatory APCs, which were primarily cDC2s. These inflammatory cDC2s expanded by helminth infection did not present dietary antigens, thus avoiding diet-specific Th2 responses.