The gastrointestinal tract constantly encounters food particles and bacteria capable of triggering an immune reaction. In normal conditions, specialised immune cells, called peripherally induced regulatory T cells (pTreg cells), help prevent unnecessary inflammation and ensure the body tolerates food and beneficial microbes. However, until now, no one has understood exactly which immune cells are responsible for food-specific tolerance.
A new study has identified a previously unknown type of antigen-presenting cell (APC) that is crucial for training pTreg cells to recognise and tolerate food and gut microbes. These APCs require two key genes, Prdm16 and RORγt, for their function, and they are distinct from all other immune cells previously studied. The cells have been named “Prdm16+ RORγt+ tolerizing dendritic cells”, abbreviated to tolDCs.
In studying the new cells within a mouse model, researchers have found that when tolDCs were disrupted, mice immune systems failed to generate pTreg cells, leading to increased allergic responses to food. This suggests that tolDCs are essential in preventing food allergies and immune disorders. The researchers also found evidence of similar cells in human tissue, indicating this food-tolerance mechanism is most likely conserved across species. Understanding how these cells work could open new avenues for treating autoimmune diseases and allergies.
Reference: Fu, L., et al. Prdm16-dependent antigen-presenting cells induce tolerance to gut antigens. Nature (2025). https://doi.org/10.1038/s41586-025-08982-4
