Rice-derived glucosylceramides activate innate immune responses in myeloid lineage differentiated dendritic cells via toll-like receptors 2 and 4

Rice-derived glucosylceramides (GlcCer) consist of multiple molecules that comprise different types of sphingoid Bases and saturated fatty acids. These GlcCer are critical for epidermal barrier function and exert anti-melanogenic effects. Regarding their effects on the immune system, a dead cell-derived GlcCer [d18:2/24:1] was shown to enhance the activation of antigen-presenting cells via Mincle receptors. However, the immunomodulatory effects of rice-derived GlcCer have yet to be examined. Therefore, we herein investigated the effects of rice-derived GlcCer on dendritic cell (DC) activation. Among rice-derived GlcCer, GlcCer[d18:2(4E,8Z)/18:0] (10 μM) significantly enhanced IL-6 production by iMylc DC established from induced pluripotent stem cells. CD40 and CD80 expression was significantly upregulated by GlcCer[d18:2(4E,8Z)/18:0] in aMylc DC derived from human peripheral blood mononuclear cells. In a Toll-like Receptor (TLR) competitive binding assay using TLR antagonists, GlcCer[d18:2(4E,8Z)/18:0] bound to TLR2 and 4. The antigen-presenting abilities of GlcCer[d18:2(4E,8Z)/18:0] and GlcCer[d18:2(4E,8Z)/26:0] were confirmed by the mixed lymphocyte reaction test, which showed a significant T-cell proliferative effect. These results indicate that GlcCer[d18:2(4E,8Z)/18:0] activated DC being sensed by TLR2 and 4 and induced T-cell responses through the expression of CD40 and CD80. Therefore, the limited GlcCer molecules in rice appear to promote innate immune responses on DC.

CD40; CD80; Dendritic cell; Glucosylceramide; Mixed lymphocyte reaction; Rice; Toll-like receptor.