A coordinated cellular network regulates tolerance to food.

Area of Science:

• Immunology
• Gastroenterology
• Microbiology

Background:

• Host tolerance to dietary antigens and commensal microbes is crucial for nutrient absorption and gut health.
• Peripheral regulatory T (pTreg) cells are key mediators of this immune tolerance.
• Conventional type 1 dendritic cells (cDC1s) were previously thought to initiate dietary pTreg induction.

Purpose of the Study:

• To identify the specific antigen-presenting cells responsible for inducing food-specific pTreg cells.
• To elucidate the role of pTreg cells and cDC1s in regulating dietary CD8αβ T cell responses during homeostasis and infection.
• To understand the immune circuit governing oral tolerance and its modulation during host challenges.

Main Methods:

• Investigated the role of RORγt+ antigen-presenting cells (APCs) in inducing food-specific pTreg cells.
• Analyzed the interaction between pTreg cells and cDC1s in regulating CD8αβ T cell expansion.
• Examined the impact of infection and food poisoning on this regulatory circuit.

Main Results:

• Food-specific pTreg cells are induced exclusively by RORγt+ APCs, not by cDC1s.
• pTreg cell-cDC1 interactions during homeostasis suppress the expansion of food-specific CD8αβ T cells.
• Infection disrupts this regulation, allowing transient expansion of dietary CD8αβ T cells with effector functions.
• Following pathogen clearance, dietary CD8αβ T cells do not expand to food antigens, preserving tolerance.

Conclusions:

• A distinct circuit involving RORγt+ APCs and T cells mediates tolerance to dietary antigens.
• This circuit allows for transient protective effector responses during infection without compromising long-term oral tolerance.
• Understanding this pathway is critical for maintaining gut homeostasis and safe food consumption.