Dietary flavonoid naringenin induces regulatory T cells via an aryl hydrocarbon receptor mediated pathway

J Agric Food Chem. 2012 Mar 7;60(9):2171-8. doi: 10.1021/jf204625y. Epub 2012 Feb 22.


The aryl hydrocarbon receptor (AhR), a transcription factor mediating xenobiotic detoxification, plays a considerable role in regulatory T cell (Treg) induction. Tregs regulate the immune system, thus suppressing allergies and autoimmune diseases. This study aims to identify new types of antiallergic dietary factors, with focus on the flavonoids with potential AhR agonistic activity. Among 25 dietary flavonoid samples tested using a reporter assay, 8 showed marked induction of AhR-dependent transcriptional activity. The subsequent T cell proliferation suppression assay identified naringenin as the only sample capable of stimulating Treg induction; notably, this induction was eliminated by cotreatment with AhR antagonists. Indeed, naringenin induced CD4(+)Foxp3(+) Tregs, irrespective of the presence of the transforming growth factor-β (TGF-β), indicating that the conventional TGF-β-dependent signaling pathway might not be involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Proliferation / drug effects
  • Diet*
  • Female
  • Flavanones / administration & dosage*
  • Flavonoids / pharmacology
  • Fluorescent Antibody Technique
  • Immune Tolerance / drug effects
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Aryl Hydrocarbon / agonists
  • Receptors, Aryl Hydrocarbon / antagonists & inhibitors
  • Receptors, Aryl Hydrocarbon / physiology*
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Transforming Growth Factor beta / pharmacology


  • Flavanones
  • Flavonoids
  • Receptors, Aryl Hydrocarbon
  • Transforming Growth Factor beta
  • naringenin