Gut immune cells found to prevent food allergy

‘Our research shows that dendritic cells expressing RORγt are key components of the immune-regulatory response that prevents food allergies’, says lead researcher Dan L. Littman. Photo: Juliana Thomas

Specialised immune cells in the gut prevent immune reactions to food by recruiting regulatory rather than pro-inflammatory cells.

A specific group of immune cells in the gut suppresses immune responses to food, according to an American study published in Nature on 14 April. The gastrointestinal tract is constantly exposed to foreign substances that could potentially trigger immune responses. Although the immune system is well known for responding to harmful invaders whilst simultaneously tolerating healthy host cells and other harmless stimuli, it has until now remained largely unclear how the system achieves this tolerance towards innocuous substances. The research team at NYU Langone Health in New York used surface marker and gene expression analyses to demonstrate how a specialised type of immune cell – so-called tolerogenic dendritic cells – ensures that food can pass through the body without triggering an immune response. When the researchers genetically disrupted tolerogenic dendritic cells in mice, the animals became more susceptible to developing food allergies and asthma.

Dendritic cells typically present foreign molecules to other immune cells, such as T cells, enabling an immune cell to mount a defence response upon renewed exposure to that same molecule. When a so-called tolerogenic dendritic cell presents a food molecule to a T cell, however, that T cell instead becomes anti-inflammatory, or regulatory: when the T cell subsequently encounters the previously presented molecule again, it does not launch an attack but instead suppresses an inflammatory response. The study shows that mice lacking properly functioning tolerogenic dendritic cells have more pro-inflammatory T cells rather than regulatory T cells.

The New York researchers had previously shown that the same type of cells also directs immune tolerance towards benign gut bacteria that help digest food and play a role in regulating various organ systems. The recent study in Nature reveals that these cells likewise control tolerance to other substances. By analysing lymph node tissue from a human organ donor, as well as multiple samples of human intestinal tissue and tonsils, the researchers also identified human equivalents of the tolerogenic dendritic cells found in mice. In an accompanying press release, one of the authors notes that it remains unclear to what extent these cells are present in the human body and whether they are also involved in immune tolerance outside the gut. Future research will need to establish how and where tolerogenic dendritic cells develop in the body and what signals they require to perform their function properly. In time, these findings could lead to innovative ways of treating food allergies, autoimmune diseases, and immune reactions in organ transplantation.