Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia;
J Immunol. 2014 Mar 1;192(5):2202-9. doi: 10.4049/jimmunol.1302040. Epub 2014 Jan 31.
Although multiple dendritic cell (DC) subsets have the potential to induce Th17 differentiation in vitro, the key DC that is critical in Th17 induction and Th17-mediated disease remains moot. In this study, we revealed that CCR2(+) monocyte-derived DCs (moDCs), but not conventional DCs, were critical for in vivo Th17 induction and autoimmune inflammation. Functional comparison in vitro indicated that moDCs are the most potent type of Th17-inducing DCs compared with conventional DCs and plasmacytoid DCs. Furthermore, we demonstrated that the importance of GM-CSF in Th17 induction and Th17-mediated disease is its endowment of moDCs to induce Th17 differentiation in vivo, although it has little effect on moDC numbers. Our findings identify the in vivo cellular targets that can be selectively manipulated to ameliorate Th17-mediated inflammatory diseases, as well as the mechanism of GM-CSF antagonism in such diseases.
尽管多种树突状细胞（DC）亚群具有体外诱导 Th17 分化的潜力，但在 Th17 诱导和 Th17 介导的疾病中起关键作用的关键 DC 仍存在争议。在这项研究中，我们揭示了 CCR2（+）单核细胞衍生的 DC（moDC），而不是常规 DC，对于体内 Th17 诱导和自身免疫炎症至关重要。体外功能比较表明，与常规 DC 和浆细胞样 DC 相比，moDC 是最有效的 Th17 诱导性 DC 类型。此外，我们证明 GM-CSF 在 Th17 诱导和 Th17 介导的疾病中的重要性在于其赋予 moDC 诱导体内 Th17 分化的能力，尽管它对 moDC 数量几乎没有影响。我们的研究结果确定了可以选择性操作的体内细胞靶标，以改善 Th17 介导的炎症性疾病，以及 GM-CSF 在这些疾病中的拮抗机制。
