Miquelianin Inhibits Allergic Responses in Mice by Suppressing CD4+ T Cell Proliferation.

Dae Woon Choi,Hee Soon Shin,Gun-Dong Kim,Sun Young Jung,So-Young Lee

doi:10.3390/antiox10071120

Dae Woon Choi, Hee Soon Shin + Show 3 more

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https://doi.org/10.3390/antiox10071120

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Abstract

Allergic diseases, including atopic dermatitis (AD), induce type 2 helper T (Th2) cell-dominant immune responses. Miquelianin (quercetin 3-O-glucuronide, MQL) is an active compound in Rosae multiflorae fructus extract with anti-allergic properties. Here, we investigate the anti-allergic effects of MQL in an ovalbumin (OVA)-induced Th2-dominant mouse model and the associated mechanisms. Oral MQL suppressed cytokine and IL-2 production and proliferation of Th2 cells and upregulated heme oxygenase-1 (HO-1) in splenocytes. Ex vivo MQL suppressed Th1- and Th2-related immune responses by inhibiting CD4+ T cell proliferation, and upregulated HO-1 in CD4+ T cells by activating C-Raf–ERK1/2–Nrf2 pathway via induction of reactive oxygen species generation. In a trimellitic anhydride-induced AD-like mouse model, both topical and oral MQL ameliorated AD symptoms by suppressing Th2 immune responses. Our results suggest that MQL is a potential therapeutic agent for CD4+ T cell-mediated diseases, including allergic diseases.

Highlights

Allergic diseases, such as allergic rhinitis, asthma, food allergy, atopic dermatitis (AD), allergic contact dermatitis, and anaphylaxis, contribute to the rising cost of health care and result in a lower quality of life
We have previously shown that Rosae multiflorae fructus extract ameliorates OVAinduced allergic rhinitis symptoms in a mouse model and identified MQL as the active compound of Rosae multiflorae fructus [21]
We examined whether oral administration of MQL affects Th2-related allergic immune responses using an OVA-induced mouse model of allergy

Summary

Introduction

Allergic diseases, such as allergic rhinitis, asthma, food allergy, atopic dermatitis (AD), allergic contact dermatitis, and anaphylaxis, contribute to the rising cost of health care and result in a lower quality of life. Allergy is characterized by immune responses mediated by antigen-specific type 2 helper T (Th2) cells that are involved in the development of antigenspecific immunoglobulin E (IgE) responses produced following class switching of B cells [1]. T cell receptors (TCRs) in naïve CD4+ T cells recognize antigens upon co-stimulation by CD28 when contacting antigen-presenting cells (APCs). Naïve CD4+ T cells can differentiate into at least four subtypes, including Th1, Th2, Th17, and induced regulatory T (iTreg) cells [4]. Among these CD4+ T cells subsets, Th2 cells are characterized by their production of interleukin (IL)-4, IL-5, and IL-13 and stimulate B cell class switching to produce antigen-specific

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