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bioRxiv · 10.1101/2023.04.11.536475

Dietary protein shapes the profile and repertoire of intestinal CD4+ T cells

Lockhart, A.·Reed, A.·de Castro, T. B. R.·Herman, C.·Canesso, M. C. C.·Mucida, D.
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Abstract

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.

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Lockhart, A., Reed, A., de Castro, T. B. R., Herman, C., Canesso, M. C. C., Mucida, D.. 2023-04-13. Dietary protein shapes the profile and repertoire of intestinal CD4+ T cells. https://doi.org/10.1101/2023.04.11.536475

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