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RORing for oral tolerance.

Cecilia Johansson¹

¹National Heart and Lung Institute, Imperial College London, London, UK.

Science (New York, N.Y.)

|July 17, 2025

Summary

A specific antigen-presenting cell subtype helps regulate the immune system's reaction to food antigens during early development. This finding is crucial for understanding immune tolerance in infants.

Area of Science:

Immunology
Developmental Biology
Allergy Research

Background:

Early life exposure to food antigens is critical for developing immune tolerance.
Dysregulation of immune responses to food can lead to allergies and intolerances.
Antigen-presenting cells (APCs) play a key role in initiating and shaping immune responses.

Purpose of the Study:

To identify specific antigen-presenting cell subtypes involved in early life immune responses to food.
To elucidate the mechanisms by which these APCs modulate the immune system towards tolerance.
To understand the implications for preventing food allergies.

Main Methods:

Flow cytometry and single-cell RNA sequencing were used to characterize APC populations in neonatal tissues.

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In vitro co-culture systems were established to assess the immunomodulatory capacity of identified APCs.

Murine models of food antigen exposure were utilized to study in vivo immune responses.

Main Results:

A distinct subset of dendritic cells was identified as a key regulator of oral immune tolerance.
These APCs actively suppressed T cell proliferation and promoted the development of regulatory T cells.
Depletion of this APC subset resulted in heightened inflammatory responses to food antigens.

Conclusions:

Specific antigen-presenting cell subtypes are essential for establishing immune tolerance to food antigens in early life.
Targeting these APCs may offer a novel therapeutic strategy for preventing and treating food allergies.
This research provides fundamental insights into the developmental programming of the immune system.