In a mouse model, LMU researchers have discovered a signaling pathway through which diet influences the development of the immune system.

The early period of life is a critical phase in which the immune system must learn to tolerate harmless environmental stimuli, such as food and microbes that normally live in and on the body, while remaining vigilant against harmful substances and pathogens. If it fails to strike the right balance, the individual may become more susceptible later in life to allergies and autoimmune diseases. During this sensitive window, the transition from breastfeeding to solid food represents a crucial shift, including in 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 signals from their environment, they shape how other immune cells, including T cells, respond to these substances. A team led by Professor Barbara Schraml from the Biomedical Center at LMU has now identified a signaling pathway in mice through which information about the dietary shift is transmitted to dendritic cells in the spleen, enabling them to adjust immune responses accordingly.

Immune cells are recalibrated

When young mice start eating solid, grain-based food, various types of lymphocytes (immune defense cells) respond by ramping up production of interferon-gamma. This messenger molecule triggers a signaling cascade that activates a specific population of dendritic cells in the spleen known as cDC1. This activation state is characterized by the production of the signaling molecule CXCL9. In turn, these specialized cDC1 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,” says Schraml.

Effect not dependent on gut flora

This regulatory circuit was also active in germ-free mice, the researchers emphasize. As such, it does not require the changes in the gut microbiota that tend to accompany weaning. “We haven’t yet been able to identify which specific dietary components influence the immune response,” says Schraml. “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.”

Immune cells also respond in adults

In addition, the researchers found that these cDC1 remained responsive to dietary changes in adult mice. This suggests that diet could represent a modifiable environmental stimulus capable of influencing immunity both during early life and later in adulthood. “Our results show that food provides the immune system not only with nutrients, but also with information,” says Schraml. “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.”