Regulatory mechanisms of IL-2 and IFNγ suppression by quercetin in T helper cells

Eun Sun Yu, Hyun Jung Min, Su Yeon An, Hee Yeon Won, Jeong Ho Hong, Eun Sook Hwang

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    61 Citations (Scopus)

    Abstract

    Quercetin is a popular flavonoid compound that is biosynthesized by plants; it is suggested to modulate a variety of inflammatory responses of macrophages and T lymphocytes. Oral administration of quercetin in arthritic rats dramatically diminishes clinical signs of arthritis. Moreover, quercetin ameliorates experimental autoimmune encephalomyelitis, which is associated with Th1-mediated immune responses. Like quercetin inhibits macrophage-induced cytokine production, it also blocks IL-12-dependent JAK-STAT signaling in Th cells. Despite the anti-inflammatory effects of quercetin acting through Th cells, the regulatory mechanisms remain unclear. Here, we studied the function of quercetin in Th cells and found that quercetin suppressed both IFNγ and IL-2 production upon T cell receptor stimulation. Furthermore, we uncovered the regulatory mechanisms of quercetin involved in the inhibition of cytokine production during Th cell activation. The fact that quercetin-derived IFNγ suppression was blocked in T-bet-deficient Th cells demonstrated quercetin act through the modulation of T-bet expression. Whereas IL-2 inhibition by quercetin was independent of T-bet expression, quercetin diminished IL-2Rα expression, which is critical for positive regulatory loop of IL-2 autoactivation. Taken together, quercetin is suggested to repress both IFNγ and IL-2 cytokine production by independent mechanisms; T-bet-dependent IFNγ suppression and IL-2Rα-dependent IL-2 inhibition.

    Original languageEnglish
    Pages (from-to)70-78
    Number of pages9
    JournalBiochemical Pharmacology
    Volume76
    Issue number1
    DOIs
    Publication statusPublished - 2008 Jul 1

    Bibliographical note

    Funding Information:
    We thank Dr. Laurie H. Glimcher for kindly providing T-bet-transgenic/deficient mice and Aging Tissue Bank for distributing anti-aging compounds. This work was partly supported by Seoul R&BD program (10642, for ESH), National R&D program for Cancer Control of National Cancer Center (0620380, for ESH), Grants for Interdisciplinary Research of KOSEF (R01-2006-000-10429), and the second stage of the Brain Korea 21 Project (for HJM, HNJ, and SJB). This work was also supported by NCRC program of MOST and KOSEF (R15-2006-020).

    Keywords

    • IFNγ
    • IL-2
    • Quercetin
    • T-bet
    • Th1

    ASJC Scopus subject areas

    • Biochemistry
    • Pharmacology

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