Study Finds Diet Shapes Immune System Development in Mice

Researchers at LMU have identified a signaling pathway in mice through which diet influences the development of the immune system. Early life is a critical period in which the immune system must learn to tolerate harmless substances, such as food and the microbes that normally live in and on the body, while remaining alert to harmful pathogens. Failing to strike this balance can make an individual more susceptible to allergies and autoimmune disease later in life. The transition from breastfeeding to solid food is a particularly important shift during this window, including for its effects on the immune system.

Dendritic cells are specialized immune cells that take up and process material from their surroundings, including components of pathogens, food and other environmental sources. By integrating these signals, dendritic cells shape how other immune cells, including T cells, respond to these substances. A team led by Professor Barbara Schraml identified a signaling pathway in mice that relays information about the dietary shift to dendritic cells in the spleen, allowing them to adjust immune responses accordingly. Their findings were published in Nature Communications.

When young mice begin eating solid, grain-based food, various lymphocytes respond by increasing production of interferon-gamma. This messenger molecule triggers a signaling cascade that activates a population of dendritic cells in the spleen known as cDC1, marked by production of the signaling molecule CXCL9. These activated cDC1 then influence the properties and activity of CD8 T cells that recognize substances derived from food. “Dietary signals are thus relayed through the immune system, helping to recalibrate the developing pool of T cells as the immune system comes into contact with a greater variety of substances from food and the environment,” Schraml said.

The researchers found this regulatory circuit was also active in germ-free mice, indicating it does not depend on the changes in gut microbiota that typically accompany weaning. “We haven’t yet been able to identify which specific dietary components influence the immune response,” Schraml said. “Possible candidates are bioactive substances found in conventional grain feed. These include components of cereal grains such as beta-glucans, as well as traces of molecules derived from microbes, such as lipopolysaccharide.”

The team also found that cDC1 remained responsive to dietary changes in adult mice, suggesting diet could be a modifiable environmental stimulus that influences immunity both in early life and adulthood. “Our results show that food provides the immune system not only with nutrients, but also with information,” Schraml added. “The discovery that cDC1 remain responsive to dietary changes in adults opens up the long-term possibility of investigating whether immune responses can be influenced by targeted dietary interventions.”