RELMβ sets the threshold for microbiome-dependent oral tolerance
Tolerance to dietary antigens is critical for avoiding deleterious type 2 immune responses resulting in food allergy (FA) and anaphylaxis1. However, the mechanisms resulting in both the maintenance and failure of tolerance to food antigens are poorly understood.
Here we demonstrate that the goblet-cell-derived resistin-like molecule β (RELMβ) is a critical regulator of oral tolerance. RELMβ is abundant in the sera of both patients with FA and mouse models of FA. Deletion of RELMβ protects mice from FA and the development of food-antigen-specific IgE and anaphylaxis.
RELMβ disrupts food tolerance through the modulation of the gut microbiome and depletion of indole-metabolite-producing Lactobacilli and Alistipes. Tolerance is maintained by the local production of indole derivatives driving FA protective RORγt+ regulatory T (Treg) cells through activation of the aryl hydrocarbon receptor. RELMβ antagonism in the peri-weaning period restores oral tolerance and protects genetically prone offspring from developing FA later in life.
Together, we show that RELMβ mediates a gut immune–epithelial circuit regulating tolerance to food antigens—a novel mode of innate control of adaptive immunity through microbiome editing—and identify targetable candidates in this circuit for prevention and treatment of FA.
For more information:
Stephen-Victor, E., Kuziel, G.A., Martinez-Blanco, M. et al. RELMβ sets the threshold for microbiome-dependent oral tolerance. Nature (2025).
Latest articles
- NOT ONLY THE GUT MICROBIOTA: THE IMPORTANCE OF THE BODY AXES
- ECOLOGY AND BALANCE OF THE GUT MICROBIOTA
- THE CONCEPT OF “SPECIES-SPECIFICITY”
- KNOW YOUR MICROBES: LOCATION, DISTRIBUTION AND FEATURES
- THE CIRCLE OF LIFE OF THE GUT MICROBIOTA
- NOURISH THE GUT MICROBIOTA EFFICIENTLY
- THE GUT MICROBIOTA
- Genus, families and strains
- The history of microbiota
- Bacteria and micronutrients