Intestinal uptake regulates T cell responses to dietary antigens

Dietary proteins can trigger both oral tolerance and food allergies, depending on how the immune system responds to them. While mouse models often use purified proteins for tolerance studies, they typically rely on antigen context and adjuvant signaling. Previous research found that the maize protein zein stimulates robust antigen-specific intestinal Tregs when exposed to normal chow but not when delivered as a purified protein.

In this study, the researchers examined why zein induces different T cell responses based on its form. They compared three zein preparations that resulted in varying frequencies of antigen-specific intestinal T cells. While in vitro tests showed similar presentation by dendritic cells, in vivo experiments uncovered significant differences in intestinal uptake.

The study identified that protein solubility and active sampling mechanisms were key factors in determining intestinal uptake. Zein could be sampled by goblet cells, which were previously linked to the model antigen OVA, or by M cells, a mechanism believed to be involved in dietary protein transport and established for pathogenic bacteria.

This finding also applies to peanuts, where the allergen Ara h 1 is selectively transported by goblet or M cells depending on food preparation, acting as a natural example of dietary M cell ligands.

Additionally, the researchers discovered that solubilizing zein enhanced intestinal uptake and led to more intestinal zein-specific T cells when fed to the diet compared to the insoluble form. These findings suggest that the intestinal uptake of dietary antigens is a regulated and context-dependent factor in determining antigen-specific T cell induction, which has implications for developing tolerance-restoring immunotherapies.