Miquelianin inhibits allergic responses in mice by suppressing CD4+ T
cell proliferation
Abstract
Background. Allergic disorders such as atopic dermatitis (AD), allergic
rhinitis, asthma, and food allergy show a predominant immune response by
type 2 helper T (Th2) cells. We previously revealed that Rosae
multiflorae fructus extract ameliorates ovalbumin-induced allergic
rhinitis symptoms in a mouse model and identified miquelianin (quercetin
3-O-glucuronide, MQL) as the active compound. However, it is unknown if
MQL affects allergic diseases or regulates Th2 immune responses. In this
study, we investigated the anti-allergic effects of MQL. Methods. To
investigate anti-allergic effects of MQL, we used an ovalbumin
(OVA)-induced Th2-dominant mouse model and assessed cytokine production,
cell proliferation, and upstream signaling pathways. Results. Oral
administration of MQL suppressed the production of Th2 cytokines and
IL-2, and cell proliferation. Additionally, heme oxygenase-1 (HO-1)
expression was increased by MQL in splenocytes. In ex vivo studies using
splenocytes and CD4+ T cells from mice, MQL suppressed Th1- and
Th2-related immune responses by inhibiting CD4+ T cell proliferation.
Furthermore, MQL increased HO-1 expression by activating the C-Raf
-ERK1/2-NRF2 pathway by inducing the generation of intracellular
reactive oxygen species in CD4+ T cells. Finally, to verify the effects
of MQL in vivo during an allergic disorder, we used a trimellitic
anhydride-induced AD-like mouse model. Both topical treatment and oral
administration of MQL ameliorated AD symptoms by suppressing Th2 immune
responses, including serum IgE production Th2 cytokine production in
draining lymph nodes. Conclusions. MQL can be used as a therapeutic
agent for CD4+ T cell-mediated diseases such as allergic diseases.