Kodama Naoki, Okada Hikaru, Hachisu Masakazu, Ando Miki, Ito Naoto, Nagata Kazuki, Katagiri Mayuka, Yasuda Yayoi, Hiroki Ikumi, Yashiro Takuya, Ichihara Gaku, Yamamoto Masayuki, Nishiyama Chiharu
Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, Japan.
Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
Front Nutr. 2023 Feb 9;10:1081263. doi: 10.3389/fnut.2023.1081263. eCollection 2023.
Dendritic cells (DCs), which are typical antigen-presenting cells, localize to various sites in the body, particularly the front line of infection as sentinels, and are involved in innate and adaptive immune responses. Although the functions of DCs, such as pathogen-induced cytokine production and antigen-specific T cell activation, are important for host defenses against infection and tumorigenesis, the hyper- and/or extended activation of DCs leads to inflammatory and autoimmune diseases. In the present study, β-damascone, a major ingredient of rose fragrance, was selected from an aroma library as a candidate compound that suppresses antigen-induced immune responses. β-Damascone inhibited the functions of DCs, including the antigen-dependent proliferation of T cells, DC-induced Th1 development, and the TLR ligand-induced production of inflammatory cytokines by DCs. The β-damascone treatment also increased the protein level of the transcription factor NF-E2-related factor 2 (NRF2), which plays key roles in antioxidant responses, and the transcription of and , target genes of NRF2, in DCs. DCs induced Th1-development and produced large amount of IL-12p40 even in the presence of β-damascone, whereas these functions by DCs were inhibited by β-damascone under the same conditions. The intake of β-damascone suppressed ear swelling in contact hypersensitivity (CHS) model mice, but not in CHS-induced mice. Collectively, the present results indicate the potential of the rose aroma compound β-damascone, which suppresses DC-mediated immune responses by activating the NRF2 pathway in DCs, for the prevention and/or attenuation of immune-mediated diseases.
树突状细胞（DCs）是典型的抗原呈递细胞，定位于体内的各个部位，尤其是作为哨兵的感染前线，并参与先天性和适应性免疫反应。尽管DCs的功能，如病原体诱导的细胞因子产生和抗原特异性T细胞活化，对宿主抵御感染和肿瘤发生很重要，但DCs的过度和/或持续激活会导致炎症和自身免疫性疾病。在本研究中，从香气库中选择玫瑰香味的主要成分β-大马酮作为抑制抗原诱导免疫反应的候选化合物。β-大马酮抑制了DCs的功能，包括T细胞的抗原依赖性增殖、DC诱导的Th1细胞发育以及DCs由TLR配体诱导的炎症细胞因子产生。β-大马酮处理还增加了转录因子NF-E2相关因子2（NRF2）的蛋白水平，NRF2在抗氧化反应中起关键作用，并且增加了DCs中NRF2的靶基因 和 的转录。即使在存在β-大马酮的情况下，DCs仍诱导Th1细胞发育并产生大量IL-12p40，而在相同条件下， DCs的这些功能被β-大马酮抑制。在接触性超敏反应（CHS）模型小鼠中，摄入β-大马酮可抑制耳部肿胀，但在CHS诱导的 小鼠中则不然。总体而言，本研究结果表明玫瑰香气化合物β-大马酮具有通过激活DCs中的NRF2途径来抑制DC介导的免疫反应的潜力，可用于预防和/或减轻免疫介导的疾病。
