Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan.
Department of Health Administration, Tzu Chi University of Science and Technology, Hualien, Taiwan.
Am J Chin Med. 2019;47(6):1271-1287. doi: 10.1142/S0192415X19500654. Epub 2019 Sep 5.
Dendritic cells (DCs) play a critical role in initiating immune responses; however, DCs also induce Th2-related allergic sensitivities. Thus, DCs become a target for therapeutic design in allergic diseases. In this study, we aim to investigate the anti-allergic effect of pure compounds from a medicinal mushroom (Ac) on DC-induced allergic responses. We identified a benzenoid compound 4,7-dimethoxy-5-methyl-l,3-benzodioxole (DMB) which may modulate Th2 polarization in bone marrow-derived DCs (BMDCs) and in a murine food allergy model. DMB effectively reduced the Th2 adjuvant cholera toxin (CT)-induced BMDC maturation and cytokine production. In studying the mechanism, DMB blocked the molecular processes involved in Th2 induction, including cAMP activation, IL-33 production, and IRF4/Tim4 upregulation, in CT-activated BMDCs. Furthermore, DMB treatment attenuated the symptoms, clinical scores, and Th2 responses of CT-induced ovalbumin (OVA)-specific food allergy in mice at sensitization stage. These results indicated that DMB could suppress DC function for Th2 polarization and mitigate allergic responses. Thus, DMB may have potential to be a novel agent for preventing or treating food allergy.
树突状细胞 (DCs) 在启动免疫反应中发挥着关键作用；然而，DCs 也会诱导与 Th2 相关的过敏敏感性。因此，DCs 成为过敏疾病治疗设计的目标。在这项研究中，我们旨在研究一种药用蘑菇（Ac）中的纯化合物对 DC 诱导的过敏反应的抗过敏作用。我们鉴定出一种苯并呋喃类化合物 4,7-二甲氧基-5-甲基-1,3-苯并二恶唑（DMB），它可能调节骨髓来源的树突状细胞（BMDCs）和小鼠食物过敏模型中的 Th2 极化。DMB 有效降低了 Th2 佐剂霍乱毒素 (CT) 诱导的 BMDC 成熟和细胞因子产生。在研究机制时，DMB 阻断了 CT 激活的 BMDCs 中涉及 Th2 诱导的分子过程，包括 cAMP 激活、IL-33 产生和 IRF4/Tim4 上调。此外，DMB 治疗在致敏阶段减轻了 CT 诱导的卵清蛋白 (OVA) 特异性食物过敏小鼠的症状、临床评分和 Th2 反应。这些结果表明，DMB 可以抑制 DC 功能以促进 Th2 极化并减轻过敏反应。因此，DMB 可能具有预防或治疗食物过敏的潜力。
