biostudies-literatureLockhart AFood Allergy FARE/FASI ConsortiumHoward Hughes Medical Institutee20221816https://www.ebi.ac.uk/biostudies/studies/S-EPMC10192604biostudies-literatureUnknown220(8)The intestinal immune system must tolerate food antigens to avoid allergy, a process requiring CD4+ T cells. Combining antigenically defined diets with gnotobiotic models, we show that food and microbiota distinctly influence the profile and T cell receptor repertoire of intestinal CD4+ T cells. Independent of the microbiota, dietary proteins contributed to accumulation and clonal selection of antigen-experienced CD4+ T cells at the intestinal epithelium, imprinting a tissue-specialized transcriptional program including cytotoxic genes on both conventional and regulatory CD4+ T cells (Tregs). This steady state CD4+ T cell response to food was disrupted by inflammatory challenge, and protection against food allergy in this context was associated with Treg clonal expansion and decreased proiThe Journal of experimental medicineDietary protein shapes the profile and repertoire of intestinal CD4+ T cells.PMC10192604R01DK113375R01DK093674R21AI144827Rezende de Castro TCampos Canesso MCMucida DHerman CLockhart AReed AfalseDietary protein shapes the profile and repertoire of intestinal CD4+ T cells.The intestinal immune system must tolerate food antigens to avoid allergy, a process requiring CD4+ T cells. Combining antigenically defined diets with gnotobiotic models, we show that food and microbiota distinctly influence the profile and T cell receptor repertoire of intestinal CD4+ T cells. Independent of the microbiota, dietary proteins contributed to accumulation and clonal selection of antigen-experienced CD4+ T cells at the intestinal epithelium, imprinting a tissue-specialized transcriptional program including cytotoxic genes on both conventional and regulatory CD4+ T cells (Tregs). This steady state CD4+ T cell response to food was disrupted by inflammatory challenge, and protection against food allergy in this context was associated with Treg clonal expansion and decreased proi2023-01-01T00:00:00Z2023 Aug2025-04-04T23:45:03.346Z2025-04-04T23:45:03.346ZS-EPMC101926043719172010.1084/jem.20221816