Epidemiological studies associate the rapid increase in the incidence of inflammatory disorders with a 'Western lifestyle', and especially with the 'Western diet' that is characterized by processed foods and a low content of vegetables and fruits.
Shared molecular pathways between nutrient- and pathogen-sensing systems provide a potential molecular link between diet and disease. Targets at the intersection of metabolic and inflammatory responses are ligand-activated nuclear receptors and G protein-coupled receptors.
Vitamins A and D (both acting through nuclear receptors) alter lymphocyte migration and activation, thereby contributing to intestinal immune homeostasis, which is characterized by a state of tolerance towards innocuous antigens.
Plants of the Brassica genus, which includes cruciferous vegetables such as green cabbages and broccoli, contain ligands for the nuclear receptor aryl hydrocarbon receptor (AHR). AHR activity is required for the maintenance of intraepithelial lymphocytes and the proliferative capacity of postnatally developed RORγt+ innate lymphoid cells in the intestine.
Fatty acids activate G protein-coupled receptors (namely GPR120 and GPR40) and nuclear receptors (namely PPARs, LXRs and FXR) that are expressed by immune cells. Saturated fatty acids are generally thought to have a role in promoting inflammation, whereas unsaturated fatty acids have both pro-inflammatory and anti-inflammatory properties.
Dietary metabolites directly act on immune cells involved in the development, organization and function of the intestine, with wider implications for other organs. A balanced diet contributes to immune homeostasis, preventing aberrant immunity and pathology.
The function of the gastrointestinal tract relies on a monolayer of epithelial cells, which are essential for the uptake of nutrients. The fragile lining requires protection against insults by a diverse array of antigens. This is accomplished by the mucosa-associated lymphoid tissues of the gastrointestinal tract, which constitute a highly organized immune organ. In this Review, we discuss several recent findings that provide a compelling link between dietary compounds and the organization and maintenance of immune tissues and lymphocytes in the intestine. We highlight some of the molecular players involved, in particular ligand-activated nuclear receptors in lymphoid cells.
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V.B.-W. is supported by the Deutsche Forschungsgemeinschaft (DFG BR 4253/1-1 Forschungsstipendium). M.V. is supported by a UK Biotechnology and Biological Sciences Research Council Institute Strategic Programme Grant and the European Research Council (grant number 280307: Epithelial_Immunol).
The authors declare no competing financial interests.
- Nuclear receptors
A class of proteins found within cells that are responsible for sensing external cues (such as hormones) and that work with other proteins to regulate the expression of specific genes, thereby controlling the development, homeostasis and metabolism of the organism.
Lymphoid cells derived from the common lymphoid progenitor that lack expression of an antigen receptor. ILCs have important roles in innate immune responses to infectious microorganisms and in lymphoid tissue formation.
A group of nuclear receptor proteins involved in altering lipid and glucose metabolism. Their ligands include free fatty acids and eicosanoids.
A group of nuclear receptor proteins important in regulating cholesterol, fatty acid and glucose homeostasis. A ligand is oxysterol.
A member of the nuclear receptor family of transcription factors, with a role in maintaining bile acid, cholesterol and glucose homeostasis. Bile acids are natural ligands.
- Lamina propria
Connective tissue beneath the intestinal epithelium containing various myeloid and lymphoid cells.
A T cell population found within the epithelial layer of mammalian mucosal linings. This population consists of specialized subsets of cells, such as particular γδ T cell subsets and αβ CD8αα+ T cells.
- Cytochrome P450 enzymes
A superfamily of diverse enzymes involved in drug metabolism and bioactivation, accounting for a very large number of different metabolic reactions, including those for lipids, hormones and xenobiotics (such as drugs and chemicals).
- γδ T cells
A small subset of T cells that express a distinct T cell receptor on their surface consisting of a particular γ-chain, which correlates with their presence in particular tissues, coupled to a δ-chain.
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Veldhoen, M., Brucklacher-Waldert, V. Dietary influences on intestinal immunity. Nat Rev Immunol 12, 696–708 (2012). https://doi.org/10.1038/nri3299
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