Dietary flavonoid naringenin induces regulatory T cells via an aryl hydrocarbon receptor mediated pathway.
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.
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Hsi-Kai
HK
Wang
Chen-Hao
CH
Yeh
Taku
T
Iwamoto
Hideo
H
Satsu
Makoto
M
Shimizu
Mamoru
M
Totsuka
D016475:3T3 Cells; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004032:Diet; D005260:Female; D044950:Flavanones / Q000008:administration & dosage*; D005419:Flavonoids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007108:Immune Tolerance / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D044950:Flavanones; D005419:Flavonoids; D018336:Receptors, Aryl Hydrocarbon; D016212:Transforming Growth Factor beta; C005273:naringenin