Synchronization of mothers and offspring promotes tolerance and limits allergy

Kathryn A Knoop1, Keely G McDonald1, Paige E Coughlin1

  • 1Department of Internal Medicine and.

JCI Insight
|August 8, 2020
PubMed

Insights

Maternal and infant timing is crucial for developing immune tolerance to food allergens. Synchronized early life feeding and microbial exposure establish long-lasting gut immunity, preventing allergies in children.

Area of Science:

  • Immunology
  • Pediatrics
  • Gastroenterology

Background:

  • Allergic disorders are rising in children, linked to Th2 immune responses.
  • Breastfeeding, early allergen introduction, and antibiotic avoidance reduce allergy risk.
  • The critical early-life window for these protective effects remains unclear.

Purpose of the Study:

  • To investigate the immunological mechanisms behind early-life protection against allergies.
  • To identify a specific developmental interval for establishing immune tolerance to dietary antigens.

Main Methods:

  • Identified a preweaning interval for dietary antigen assimilation by the colonic immune system.
  • Studied maternal control of this interval via breast milk composition.
  • Examined the role of naive T cell influx and regulatory T cell (Treg) development in the colon.

Main Results:

  • A critical preweaning interval exists for developing antigen-specific colonic Tregs (pTregs).
  • Maternal-offspring desynchronization during this interval led to Treg deficits and impaired tolerance.
  • These deficits resulted in spontaneous Th2 responses and increased allergy risk.
  • Deficits were rescued by transferring periweaning colonic pTregs or in vitro generated Tregs.

Conclusions:

  • Maternal-offspring synchronization during a specific preweaning interval is essential for immune tolerance.
  • This synchronization promotes the development of long-lived, diet-specific colonic Tregs.
  • Disruptions can lead to allergies, highlighting the importance of early-life immune programming.

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