Immunomodulatory effects of D-allose on cytokine production by plasmacytoid dendritic cells 形質細胞様樹状細胞によるサイトカイン産生に対するD-アロースの免疫調整効果
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著者
書誌事項
- タイトル
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Immunomodulatory effects of D-allose on cytokine production by plasmacytoid dendritic cells
- タイトル別名
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形質細胞様樹状細胞によるサイトカイン産生に対するD-アロースの免疫調整効果
- 著者名
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髙尾, 健二郎
- 学位授与大学
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香川大学
- 取得学位
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博士(医学)
- 学位授与番号
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甲第816号
- 学位授与年月日
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2022-12-27
注記・抄録
D-Allose is classified as a 'rare sugar,' i.e., part of the group of monosaccharides that are present in low quantities in the natural world. D-Allose has been demonstrated to exert many physiological functions. The effects of the rare sugars on immune responses are largely unexplored. Here, we investigated the physiological effects of D-allose on murine dendritic cells' cytokine production. When plasmacytoid dendritic cells (pDCs) were stimulated with a Toll-like receptor 7 (TLR7) ligand, a single-stranded RNA (ssRNA), or a TLR9 ligand, CpG DNA, in the medium containing D-allose, the productions of both interferon-alpha (IFN-α) and interleukin (IL)-12p40 were severely decreased. In contrast, a normal production of these cytokines was observed when pDCs were stimulated with other TLR7 ligands, an imidazoquinoline, or a guanosine analog. In contrast to the pDCs, conventional dendritic cells (cDCs) produced IL-12p40 and tumor necrosis factor-alpha (TNF-α) in response to an imidazoquinoline or CpG DNA even though D-allose was present in the medium. D-Allose did not induce pDC death, and not inhibit the endocytic uptake of fluorophore-labeled CpG DNA into pDCs. These results suggested that D-allose exerts its inhibitory effects after CpG DNA is internalized. We analyzed the TLR7/9 signal-induced activation of downstream signaling molecules in pDCs and observed that when pDCs were stimulated with a ssRNA or CpG DNA, the phosphorylation status of the MAPK family, which includes Erk1/2, JNK/SAPK, and p38 MAPK, was attenuated in the presence of D-allose compared to D-glucose controls. The stimulation of pDCs with an imidazoquinoline induced a strong phosphorylation of these MAPK family members even in the presence of D-allose. These findings reveal that D-allose can inhibit the cytokine production by pDCs stimulated with ssRNA or CpG DNA via an attenuation of the phosphorylation of MAPK family members.
科研費 基盤研究(C) 21K08458