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<p>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(4<i>E</i>,8<i>Z</i>)/18:0] (10&#xa0;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(4<i>E</i>,8<i>Z</i>)/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(4<i>E</i>,8<i>Z</i>)/18:0] bound to TLR2 and 4. The antigen-presenting abilities of GlcCer[d18:2(4<i>E</i>,8<i>Z</i>)/18:0] and GlcCer[d18:2(4<i>E</i>,8<i>Z</i>)/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(4<i>E</i>,8<i>Z</i>)/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.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2025年10月24日

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  • Kenchi Miyasaka,
  • Shogo Takeda,
  • Ong Guang,
  • Kiyoe Itoi,
  • Kazuo Miyazaki,
  • Yoshiaki Manse,
  • Toshio Morikawa,
  • Hiroshi Shimoda

摘要

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.

Graphical abstract