LIPS induces rapid IL-10 release by M-CSF-conditioned tolerogenic dendritic cell precursors
LIPS induces rapid IL-10 release by M-CSF-conditioned tolerogenic dendritic cell precursors
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DOI：
10.1189/jlb.0406267
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发表时间：
2007-07-01
影响因子：
5.5
通讯作者：
Mueller, Chris G. F.
中科院分区：
文献类型：
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作者：
Kwan, Wing-Hong;Boix, Charlotte;Mueller, Chris G. F.
通过在 GM-CSF 中培养骨髓前体获得的树突状细胞 (DC) 会成熟，并在受到微生物产品刺激时诱导有效的 T 细胞反应。 DC 前体本身也能识别微生物产物，这些受刺激的 DC 前体如何调节免疫反应仍然是核心问题。我们在此表明，M-CSF 条件化的人 DC 前体通过快速而强劲地产生 IL-10 来响应 LPS、牛分枝杆菌和炎症细胞因子，这大大优于在未成熟 DC 或单核细胞中观察到的结果。内源性 IL-10 抑制 DC 前体转化为专业 APC，因为在 LPS 存在下阻断 IL-10 受体会导致有效 T 细胞刺激剂的形成。 LPS刺激与DC分化同时产生未成熟的DC，其能够耐受二次LPS暴露。此外，LPS激活的DC前体减少了旁观者DC的成熟和抗CD3/CD28触发的T细胞激活。这些数据表明，当暴露于炎症或微生物信号时，M-CSF条件性DC前体可以参与调节炎症和免疫反应，快速释放IL-10。
Dendritic cells (DC) obtained by culturing myeloid precursors in GM-CSF undergo maturation and induce an efficient T cell response when stimulated with microbial products. DC precursors themselves also recognize microbial products, and it remains nuclear how these stimulated DC precursors modulate the immune response. We show here that M-CSF-conditioned human DC precursors responded to LPS, Mycobacteria bovis, and inflammatory cytokines by a rapid and robust production of IL-10, largely superior to that observed with immature DC or monocytes. The endogenous IL-10 restrained the DC precursors from converting into professional APC, as blocking the IL-10 receptor in the presence of LPS resulted in the formation of efficient T cell stimulators. LPS stimulation concomitant with DC differentiation gave rise to immature DC, which were tolerant to a secondary LPS exposure. Furthermore, the LPS-activated DC precursors reduced bystander DC maturation and anti-CD3/CD28-triggered T cell activation. These data suggest that when exposed to inflammatory or microbial signals, M-CSF-conditioned DC precursors can participate in the modulation of inflammation and immune response rapid release of IL-10.