Indole-3-carbinol, a plant nutrient and AhR-Ligand precursor, supports oral tolerance against OVA and improves peanut allergy symptoms in mice

Christiane Hammerschmidt-Kamper, Daniel Biljes, Katja Merches, Irina Steiner, Thomas Daldrup, Marianne Bol-Schoenmakers, Raymond H. H. Pieters, Charlotte Esser

    Research output: Contribution to journalArticleAcademicpeer-review


    In general, dietary antigens are tolerated by the gut associated immune system. Impairment of this so-called oral tolerance is a serious health risk. We have previously shown that activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) by the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects both oral tolerance and food allergy. In this study, we determine whether a common plant-derived, dietary AhR-ligand modulates oral tolerance as well. We therefore fed mice with indole-3-carbinole (I3C), an AhR ligand that is abundant in cruciferous plants. We show that several I3C metabolites were detectable in the serum after feeding, including the high-affinity ligand 3,3´-diin-dolylmethane (DIM). I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid (RA), an inducer of regulatory T cells. We then measured parameters indicating oral tolerance and severity of peanut-induced food allergy. In contrast to the tolerance-breaking effect of TCDD, feeding mice with chow containing 2 g/kg I3C lowered the serum anti-ovalbumin IgG1 response in an experimental oral tolerance protocol. Moreover, I3C feeding attenuated symptoms of peanut allergy. In conclusion, the dietary compound I3C can positively influence a vital immune function of the gut.
    Original languageEnglish
    Article numbere0180321
    Pages (from-to)1-17
    Number of pages17
    JournalPLoS One
    Issue number6
    Publication statusPublished - 2017


    • 2,3,7,8 tetrachlorodibenzo para dioxin
    • 3 indolemethanol
    • 3,3' diindolylmethane
    • aldehyde dehydrogenase isoenzyme 1
    • aromatic hydrocarbon receptor
    • cytochrome P450 1A1
    • immunoglobulin G1 antibody
    • ovalbumin
    • retinoic acid
    • aldh1 gene
    • animal cell
    • animal experiment
    • animal model
    • animal tissue
    • article
    • catalysis
    • controlled study
    • CYP4501A1 gene
    • disease severity
    • drug efficacy
    • drug mechanism
    • experimental study
    • immune response
    • immunological tolerance
    • intestine function
    • metabolite
    • mouse
    • nonhuman
    • peanut allergy
    • regulatory T lymphocyte


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