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Related Concept Videos

Special Features of Adaptive Immunity01:20

Special Features of Adaptive Immunity

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The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
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Related Experiment Video

Updated: May 31, 2025

Quantitative Polymerase Chain Reaction-based Analyses of Murine Intestinal Microbiota After Oral Antibiotic Treatment
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RELMβ sets the threshold for microbiome-dependent oral tolerance.

Emmanuel Stephen-Victor1,2, Gavin A Kuziel2,3,4,5, Monica Martinez-Blanco1,2

  • 1Division of Immunology, Boston Children's Hospital, Boston, MA, USA.

Nature
|January 22, 2025
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Summary
This summary is machine-generated.

Resistin-like molecule beta (RELMβ) disrupts oral tolerance by altering the gut microbiome. Blocking RELMβ restores tolerance, offering a potential strategy for preventing food allergy (FA).

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Area of Science:

  • Immunology
  • Microbiome Research
  • Gastroenterology

Background:

  • Food allergy (FA) involves detrimental type 2 immune responses, but tolerance mechanisms are unclear.
  • Oral tolerance to dietary antigens is crucial for preventing FA and anaphylaxis.
  • Goblet-cell-derived resistin-like molecule beta (RELMβ) is implicated in immune regulation.

Purpose of the Study:

  • To investigate the role of RELMβ in regulating oral tolerance to food antigens.
  • To elucidate the mechanisms by which RELMβ influences food tolerance and FA development.
  • To identify potential therapeutic targets for FA prevention and treatment.

Main Methods:

  • Utilized mouse models of FA and gene deletion studies (RELMβ knockout).
  • Analyzed serum RELMβ levels in FA patients and mouse models.
  • Investigated the impact of RELMβ on gut microbiome composition and function (indole metabolism).
  • Assessed the role of indole derivatives and RORγt+ regulatory T (Treg) cells in tolerance.
  • Evaluated the therapeutic potential of RELMβ antagonism during the peri-weaning period.

Main Results:

  • RELMβ is elevated in FA patients and mouse models.
  • RELMβ deletion protected mice from FA, IgE production, and anaphylaxis.
  • RELMβ disrupted oral tolerance by depleting indole-producing Lactobacilli and Alistipes.
  • Indole derivatives promote FA-protective RORγt+ Treg cells via aryl hydrocarbon receptor activation.
  • RELMβ antagonism during weaning restored tolerance and prevented FA in susceptible mice.

Conclusions:

  • RELMβ is a critical regulator of oral tolerance, mediating a gut immune-epithelial circuit.
  • RELMβ functions through microbiome editing, impacting innate control of adaptive immunity.
  • Targeting the RELMβ-microbiome-indole-Treg axis offers a novel strategy for FA prevention and treatment.