Dietary 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. Indep...

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Bibliographic Details
Published inbioRxiv : the preprint server for biology
Main Authors Lockhart, Ainsley, Reed, Aubrey, de Castro, Tiago Rezende, Herman, Calvin, Canesso, Maria Cecilia Campos, Mucida, Daniel
Format Journal Article
LanguageEnglish
Published United States 13.04.2023
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Summary: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 pro-inflammatory gene expression. Finally, we identified both steady state epithelium-adapted CD4 T cells and tolerance-induced Tregs that recognize dietary antigens, suggesting that both cell types may be critical for preventing inappropriate immune responses to food.