Immune regulation under pressure: Effects of diet on regulatory T cells in wild house mice

The immune system is crucial for fighting infections, however, exacerbated inflammation leads to autoimmune disease, inflammatory conditions, and allergies. Maintaining this balance is particularly challenging at barrier sites, such as the gastrointestinal tract and the skin, which are constantly exposed to the outside world. Several cell types and mechanisms are involved in keeping this balance, yet regulatory T cells are considered the master regulatory cell within the body, their absence leading to fatal multi-organ inflammatory disease.

Most of our knowledge of the factors affecting immune regulation (e.g. diet, microbiome, age) stems from controlled laboratory studies using inbred mice with a minimal exposure to environmental stresses. This reductionist approach has led to major advances in our knowledge of immunology, however, many treatments developed in laboratory mice fail to provide effective therapies for humans.

This project will, for the first time, investigate what shapes immune regulation at barrier sites in a complex, real-world system, helping to bridge the gap between the lab and the wild.

This project will use a unique study population of wild house mice (Mus musculus domesticus) living on the Isle of May National Nature Reserve, UK, with minimal human interference and no terrestrial predators. As these are the same species as lab mice, in-depth immunological analysis is possible. Team-based mark-recapture studies allow the acquisition of longitudinal as well as terminal samples.

Through a dietary intervention in the field in summer and early winter, this project will explore the mechanisms driving the impact of nutrition on immune regulation at barrier sites - with particular focus on regulatory T cells - in an ecologically relevant context. The key goals of this interdisciplinary project will use this wild population of the house mouse model system to:

a. Determine how nutritional quality impact immune regulatory cells and molecules in the gastrointestinal tract and skin

b. Experimentally investigate how key environmental factors (e.g. intestinal parasites, ectoparasites, gut microbiota) and demographic factors (i.e. age, sex, reproductive condition) impact the relationship between nutrition and immune regulation

c. Use novel tools from machine learning to probe the predictive power of longitudinal biomarkers for skin and gut immune regulatory states