Curdlan Induces DC-Mediated Th17 Polarization via Jagged1 Activation in Human Dendritic Cells
Curdlan Induces DC-Mediated Th17 Polarization via Jagged1 Activation in Human Dendritic Cells
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DOI：
10.2332/allergolint.09-oa-0103
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发表时间：
2010-06-01
影响因子：
6.8
通讯作者：
Matsushita, Sho
中科院分区：
文献类型：
--
作者：
Higashi, Takehiro;Hashimoto, Kumiko;Matsushita, Sho
背景：Th17 诱导活性由某些多糖（例如源自白色念珠菌的 β-葡聚糖）携带。我们之前的研究表明，Th1 和 Th2 诱导活性可以通过 Notch 配体亚型的表达模式进行定性评估，使用人单核细胞衍生的树突状细胞 (Mo-DC) 和一些白血病细胞系（如 THP-1）。 Th17 诱导活性与 Notch 配体表达模式的关联尚不清楚。方法：将来自健康志愿者的 Mo-DC 与 HLA-DR 非共享同种异体 CD4(+) 初始 T 细胞共培养，在凝胶多糖等佐剂存在下诱导混合淋巴细胞反应。通过酶联免疫吸附测定 (ELISA) 测定培养物上清液中的 IFNγ、IL-5 和 IL-17。使用 RT-PCR 评估 Mo-DC 和 THP-1 细胞上的 Notch 配体表达。结果：本研究表明，β-葡聚糖之一的凝胶多糖具有诱导 DC 介导的 Th17 分化的能力。还有趣的是，Mo-DC 和 THP-1 细胞中的 Jagged1 mRNA 被凝乳多糖上调。此外，多克隆抗 Jagged1 抗体抑制了 DC 介导的 Th17 分化。结论：本研究表明，凝胶多糖通过 DC 中的 Jagged1 激活诱导人 DC 介导的 Th17 极化。
Background: Th17-inducing activity is carried by certain polysaccharides such as beta-glucan derived from Candia albicans. Our previous studies have shown that Th1- and Th2-inducing activities can be qualitatively evaluated by the expression patterns of Notch ligand isoforms, using human monocyte-derived dendritic cells (Mo-DCs) and some leukemic cell lines such as THP-1. The association of Th17-inducing activities with Notch ligand expression patterns has been unclear.Methods: Mo-DCs from healthy volunteers were co-cultured with HLA-DR-nonshared allogeneic CD4(+) naive T cells to induce a mixed lymphocyte reaction, in the presence of adjuvants, such as curdlan. Culture supernatants were assayed for IFN gamma, IL-5 and IL-17 by an enzyme-linked immunosorbent assay (ELISA). Notch ligand expression on Mo-DCs and THP-1 cells was evaluated by using RT-PCR.Results: The present study shows that curdlan, one of the beta-glucans, has the ability to induce DC-mediated Th17 differentiation. It is also interesting to note that Jagged1 mRNA in Mo-DCs and THP-1 cells is upregulated by curdlan. Furthermore, polyclonal anti-Jagged1 antibody inhibited such DC-mediated Th17 differentiation.Conclusions: This study suggests that curdlan induces human DC-mediated Th17 polarization via Jagged1 activation in DCs.