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Rose flavor compound b-damascone regulates dendritic cell-mediated immunoresponses by modulating the NRF2 pathway and ameliorates contact hypersensitivity
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  • Naoki Kodama,
  • Hikaru Okada,
  • Kazuki Nagata,
  • Miki Ando,
  • Naoto Ito,
  • Takuya Yashiro,
  • Gaku Ichihara,
  • Masayuki Yamamoto,
  • Masakazu Hachisu,
  • Chiharu Nishiyama
Naoki Kodama
Tokyo Rika Daigaku - Katsushika Campus
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Hikaru Okada
Tokyo Rika Daigaku - Katsushika Campus
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Kazuki Nagata
Tokyo Rika Daigaku - Katsushika Campus
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Miki Ando
Tokyo Rika Daigaku - Katsushika Campus
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Naoto Ito
Tokyo Rika Daigaku - Katsushika Campus
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Takuya Yashiro
Tokyo Rika Daigaku - Katsushika Campus
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Gaku Ichihara
Tokyo Rika Daigaku - Noda Campus
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Masayuki Yamamoto
Tohoku Daigaku Daigakuin Igaku Kenkyuka Igakubu Seibutsu Kagaku Bunya
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Masakazu Hachisu
Tokyo Rika Daigaku - Katsushika Campus
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Chiharu Nishiyama
Tokyo Rika Daigaku - Katsushika Campus

Corresponding Author:[email protected]

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Abstract

Background: Numerous pharmacologically beneficial compounds have been isolated from natural products derived from plants; these compounds are often characterized as phytochemicals and are used in flavors, spices, fragrances, and colors. In the current study, we aimed to obtain novel immunomodulators from aroma compounds. Methods: We selected a candidate that inhibits antigen-presenting cell-mediated activation of T cells from an aroma library. The molecular mechanisms by which the candidate compound modulates immunoresponses were analyzed with in vitro studies, and the biological significance of the candidate was evaluated by using a mouse model. Results: b-Damascone, a major ingredient of rose fragrance, was selected from an aroma library as a candidate compound that suppresses antigen-dependent T cell activation, through 2-step screening using OT-II splenocytes. Investigations using flow cytometry, ELISA, and qPCR revealed that b-damascone inhibited dendritic cell (DC)-related responses, including DC-induced Th1 development, TLR ligand-induced transactivation and production of inflammatory cytokines in DCs, and LPS-induced upregulation of MHC class II and CD86 on DCs. Regarding intracellular events, we found that b-damascone treatment increased the levels of NRF2 protein and Hmox1 mRNA in DCs. Nrf2 -/- DCs, in which b-damascone-induced Hmox1 transcription was not observed, possessed Th1-induction activity and higher IL-12p40 production activity even in the presence of b-damascone in comparison with Nrf2 +/- DCs. Finally, we evaluated the effect of orally administered b-damascone on the pathology of contact hypersensitivity model mice and found that b-damascone intake suppressed ear swelling. Conclusions: The rose aroma compound b-damascone, which suppresses DC-mediated immunoresponses by activating the NRF2 pathway, could be useful to ameliorate immunorelated diseases.