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 Treg cells induced from conventional T cells in the periphery (pT(reg) cells). Although orally introducing nominal protein antigens is known to induce such pTreg 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.