Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine

Dietary antigens are normally rendered nonimmunogenic through a poorly understood "oral tolerance" mechanism that involves immunosuppressive regulatory T (T_reg) cells, especially T_reg cells induced from conventional T cells in the periphery (pT_reg cells). Although orally introducing nominal protein antigens is known to induce such pT_reg cells, whether a typical diet induces a population of pT_reg cells under normal conditions thus far has been unknown. By using germ-free mice raised and bred on an elemental diet devoid of dietary antigens, we demonstrated that under normal conditions, the vast majority of the small intestinal pT_reg cells are induced by dietary antigens from solid foods. Moreover, these pT_reg cells have a limited life span, are distinguishable from microbiota-induced pT_reg cells, and repress underlying strong immunity to ingested protein antigens.