Dendritic Cell Program, Mater Medical Research Institute, South Brisbane, Queensland, Australia.
Eur J Immunol. 2012 Jun;42(6):1512-22. doi: 10.1002/eji.201142098.
Human blood myeloid DCs can be subdivided into CD1c (BDCA-1)(+) and CD141 (BDCA-3)(+) subsets that display unique gene expression profiles, suggesting specialized functions. CD1c(+) DCs express TLR4 while CD141(+) DCs do not, thus predicting that these two subsets have differential capacities to respond to Escherichia coli. We isolated highly purified CD1c(+) and CD141(+) DCs and compared them to in vitro generated monocyte-derived DCs (MoDCs) following stimulation with whole E. coli. As expected, MoDCs produced high levels of the proinflammatory cytokines TNF, IL-6, and IL-12, were potent inducers of Th1 responses, and processed E. coli-derived Ag. In contrast, CD1c(+) DCs produced only low levels of TNF, IL-6, and IL-12 and instead produced high levels of the anti-inflammatory cytokine IL-10 and regulatory molecules IDO and soluble CD25. Moreover, E. coli-activated CD1c(+) DCs suppressed T-cell proliferation in an IL-10-dependent manner. Contrary to their mouse CD8(+) DC counterparts, human CD141(+) DCs did not phagocytose or process E. coli-derived Ag and failed to secrete cytokines in response to E. coli. These data demonstrate substantial differences in the nature of the response of human blood DC subsets to E. coli.
人类血液髓样树突状细胞 (DCs) 可进一步分为 CD1c（BDCA-1）（+）和 CD141（BDCA-3）（+）亚群，它们表现出独特的基因表达谱，提示具有特殊功能。CD1c（+）DC 表达 TLR4，而 CD141（+）DC 则不表达，因此预测这两个亚群对大肠杆菌的反应能力存在差异。我们分离了高度纯化的 CD1c（+）和 CD141（+）DC，并在体外与全大肠杆菌刺激后将其与单核细胞衍生的 DC（MoDC）进行比较。正如预期的那样，MoDC 产生高水平的促炎细胞因子 TNF、IL-6 和 IL-12，是 Th1 反应的有力诱导剂，并处理大肠杆菌衍生的 Ag。相比之下，CD1c（+）DC 仅产生低水平的 TNF、IL-6 和 IL-12，而是产生高水平的抗炎细胞因子 IL-10 和调节分子 IDO 和可溶性 CD25。此外，大肠杆菌激活的 CD1c（+）DC 通过 IL-10 依赖性方式抑制 T 细胞增殖。与它们的小鼠 CD8（+）DC 对应物相反，人 CD141（+）DC 不吞噬或处理大肠杆菌衍生的 Ag，也不能响应大肠杆菌分泌细胞因子。这些数据表明，人类血液 DC 亚群对大肠杆菌的反应性质存在显著差异。
