Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life

Kathryn A. Knoop, Keely G. McDonald, Chyi Song Hsieh, Phillip I. Tarr, Rodney D. Newberry

Research output: Contribution to journalArticlepeer-review

Abstract

Atopic disorders including allergic rhinitis, asthma, food allergy, and dermatitis, are increasingly prevalent in Western societies. These disorders are largely characterized by T helper type 2 (Th2) immune responses to environmental triggers, particularly inhaled and dietary allergens. Exposure to such stimuli during early childhood reduces the frequency of allergies in at-risk children. These allergic responses can be restrained by regulatory T cells (Tregs), particularly Tregs arising in the gut. The unique attributes of how early life exposure to diet and microbes shape the intestinal Treg population is a topic of significant interest. While imprinting during early life promotes the development of a balanced immune system and protects against immunopathology, it remains unclear if Tregs that develop in early life continue to restrain systemic inflammatory responses throughout adulthood. Here, an inducible deletion strategy was used to label Tregs at specified time points with a targeted mechanism to be deleted later. Deletion of the Tregs labeled peri-weaning at day of life 24, but not before weaning at day of life 14, resulted in increased circulating IgE and IL-13, and abrogated induction of tolerance towards new antigens. Thus, Tregs developing peri-weaning, but not before day of life 14 are continually required to restrain allergic responses into adulthood.

Original languageEnglish (US)
Article number603059
JournalFrontiers in immunology
Volume11
DOIs
StatePublished - Feb 3 2021

Keywords

  • Foxp3
  • RORγT
  • allergy
  • regulatory T cells
  • weaning

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life'. Together they form a unique fingerprint.

Cite this