3.1 β-damascone was identified as an immunomodulator suppressing DC-mediated T cell activation
To find novel immunomodulators, we performed 2-step screening using an aroma-compound library (Supplementary Table SII ). By the 1st screening, in which APC-dependent T cell proliferation was assayed, 22 candidates were selected from 150 compounds as immunosuppressors, and 3 compounds were passed through the 2nd screening evaluating the suppressive effect on IL-2 release from OVA-pulsed OT-II splenocytes (Supplementary Figure S1 ). Considering several factors, such as IC50, we finally selected #177 β-damascone (Figure 1A ), a major component of rose aromas. In accordance with preliminary observations in the abovementioned screening, β-damascone suppressed OVA-induced IL-2 production from OT-II splenocytes (Figure 1B ) and APC-dependent proliferation of CD4+ T cells (Figure 1D ) in a dose-dependent manner at concentrations much lower than those showing cytotoxicity (Figure 1C ). Although APC-independent T cell proliferation caused by stimulation with plate-coated anti-CD3 and anti-CD28 Abs was moderately suppressed by β-damascone (Figure 1E ), considering that the development of Th1 cells induced by OVA-pulsed DCs (Figure 1F ) but not by CD3/CD28 stimulation (Figure 1G ) was significantly suppressed by β-damascone, we focused on the effect of β-damascone on the function of DCs.