Immunomodulatory effects of D-allose on cytokine production by plasmacytoid dendritic cells
Immunomodulatory effects of D-allose on cytokine production by plasmacytoid dendritic cells
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D-阿洛糖对浆细胞样树突状细胞产生细胞因子的免疫调节作用
DOI：
10.1016/j.bbrc.2022.08.037
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发表时间：
2022
影响因子：
3.1
通讯作者：
Hoshino Katsuaki
中科院分区：
文献类型：
--
作者：
Takao Kenjiro;Suzuki Makiko;Miyazaki Ryo;Miyake Minoru;Akimitsu Kazuya;Hoshino Katsuaki
D-Allose被归类为“稀有糖”，即在自然界中含量较低的单糖组的一部分。D-Allose已被证明具有许多生理功能。稀有糖对免疫反应的影响在很大程度上尚未被探索。在这里，我们研究了D-allose对小鼠树突状细胞细胞因子产生的生理影响。在含有D-allose的培养基中，用toll样受体7 （TLR7）配体、单链RNA （ssRNA）或TLR9配体CpG DNA刺激浆细胞样树突状细胞（pDCs）时，干扰素-α (IFN-α)和白细胞介素(IL)-12p40的产生均严重降低。相反，当其他TLR7配体、咪唑喹啉或鸟苷类似物刺激pDCs时，观察到这些细胞因子的正常产生。与pDCs相反，即使培养基中存在D-allose，传统树突状细胞（cdc）也会对咪唑喹啉或CpG DNA产生IL-12p40和肿瘤坏死因子-α (TNF-α)。D-Allose不诱导pDC死亡，也不抑制荧光团标记的CpG DNA内吞入pDC。这些结果表明，D-allose在CpG DNA内化后发挥其抑制作用。我们分析了TLR7/9信号诱导pDCs下游信号分子的激活，并观察到当pDCs被ssRNA或CpG DNA刺激时，MAPK家族（包括Erk1/2， JNK/SAPK和p38 MAPK）的磷酸化状态在D-allose的存在下与d -葡萄糖对照相比减弱。用咪唑喹啉刺激pDCs，即使在D-allose存在的情况下，也会引起这些MAPK家族成员的强烈磷酸化。这些发现表明，D-allose可以通过抑制MAPK家族成员的磷酸化来抑制ssRNA或CpG DNA刺激的pDCs产生细胞因子。
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.