Food Protein Induced Activation and Death of T Cells Is Required for Normal Development and Homeostasis of the Small Intestine

Dietary components modulate not only the microbial composition in our body but also seem to be required for the development of the gut-associated lymphoid tissue (GALT). However, the impact of dietary proteins on metabolic state and immune function of the intestinal tissue remains enigmatic. We here show that replacement of food proteins by amino acids not only alters the intestinal morphology but also affects the metabolic activity and T cell reactivity in the small intestine of mice. Pathway analysis of the gene transcripts induced by dietary proteins indicated massive alterations in lipid and fatty acid metabolism, as well as regulation of hormone levels and cholesterol absorption in the small intestine. Further, physiological uptake of dietary proteins generated highly activated CD4+CD44+Helios+ T cells, predominantly in Peyer´s patches (PP). Mice fed amino acid-containing, protein-free diet developed a highly impaired intestinal bar rier with atrophic PP and dramatically reduced numbers of activated CD4+Helios+ T cells which were increased to normal levels after switching to conventional diet. These findings demonstrate that constant recognition of food proteins is crucial for maintaining the immune homeostasis within the small intestine.