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

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Science  19 Feb 2016:
Vol. 351, Issue 6275, pp. 858-863
DOI: 10.1126/science.aac5560

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Keeping immune cells quiet on a diet

Over thousands of years, our immune systems has evolved to distinguish self from foreign, perpetrating attacks on microbes but not ourselves. Given this, why do we fail to mount an immune response against most of the food we eat? Kim et al. compared normal mice, mice lacking microbes, and mice lacking microbes that were fed an elemental diet devoid of dietary antigens (see the Perspective by Kuhn and Weiner). Dietary antigens normally induced a population of suppressive immune cells called regulatory T cells in the small intestine. The cells were distinct from regulatory T cells induced by microbial antigens and prevented strong reactions against food.

Science, this issue p. 858; see also p. 810


Dietary antigens are normally rendered nonimmunogenic through a poorly understood “oral tolerance” mechanism that involves immunosuppressive regulatory T (Treg) cells, especially Treg cells induced from conventional T cells in the periphery (pTreg cells). Although orally introducing nominal protein antigens is known to induce such pTreg cells, whether a typical diet induces a population of pTreg 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 pTreg cells are induced by dietary antigens from solid foods. Moreover, these pTreg cells have a limited life span, are distinguishable from microbiota-induced pTreg cells, and repress underlying strong immunity to ingested protein antigens.

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