Vaccine Research Center, Emory University, Atlanta, GA 30329, USA.
J Immunol. 2011 Jul 15;187(2):733-47. doi: 10.4049/jimmunol.1002701. Epub 2011 Jun 10.
Although several subsets of intestinal APCs have been described, there has been no systematic evaluation of their phenotypes, functions, and regional localization to date. In this article, we used 10-color flow cytometry to define the major APC subsets in the small and large intestine lamina propria. Lamina propria APCs could be subdivided into CD11c(+)CD11b(-), CD11c(+)CD11b(+), and CD11c(dull)CD11b(+) subsets. CD11c(+)CD11b(-) cells were largely CD103(+)F4/80(-) dendritic cells (DCs), whereas the CD11c(+)CD11b(+) subset comprised CD11c(+)CD11b(+)CD103(+)F4/80(-) DCs and CD11c(+)CD11b(+)CD103(-)F4/80(+) macrophage-like cells. The majority of CD11c(dull)CD11b(+) cells were CD103(-)F4/80(+) macrophages. Although macrophages were more efficient at inducing Foxp3(+) regulatory T (T(reg)) cells than DCs, at higher T cell/APC ratios, all of the DC subsets efficiently induced Foxp3(+) T(reg) cells. In contrast, only CD11c(+)CD11b(+)CD103(+) DCs efficiently induced Th17 cells. Consistent with this, the regional distribution of CD11c(+)CD11b(+)CD103(+) DCs correlated with that of Th17 cells, with duodenum > jejunum > ileum > colon. Conversely, CD11c(+)CD11b(-)CD103(+) DCs, macrophages, and Foxp3(+) T(reg) cells were most abundant in the colon and scarce in the duodenum. Importantly, however, the ability of DC and macrophage subsets to induce Foxp3(+) T(reg) cells versus Th17 cells was strikingly dependent on the source of the mouse strain. Thus, DCs from C57BL/6 mice from Charles River Laboratories (that have segmented filamentous bacteria, which induce robust levels of Th17 cells in situ) were more efficient at inducing Th17 cells and less efficient at inducing Foxp3(+) T(reg) cells than DCs from B6 mice from The Jackson Laboratory. Thus, the functional specializations of APC subsets in the intestine are dependent on the T cell/APC ratio, regional localization, and source of the mouse strain.
尽管已经描述了几种肠道 APC 亚群，但迄今为止，尚未对其表型、功能和区域定位进行系统评估。在本文中，我们使用 10 色流式细胞术来定义小肠和大肠固有层中的主要 APC 亚群。固有层 APC 可分为 CD11c(+)CD11b(-)、CD11c(+)CD11b(+)和 CD11c(弱)CD11b(+)亚群。CD11c(+)CD11b(-)细胞主要为 CD103(+)F4/80(-)树突状细胞（DC），而 CD11c(+)CD11b(+)亚群包括 CD11c(+)CD11b(+)CD103(+)F4/80(-)DC 和 CD11c(+)CD11b(+)CD103(-)F4/80(+)巨噬细胞样细胞。大多数 CD11c(弱)CD11b(+)细胞为 CD103(-)F4/80(+)巨噬细胞。尽管巨噬细胞比 DC 更有效地诱导 Foxp3(+)调节性 T（Treg）细胞，但在较高的 T 细胞/APC 比例下，所有 DC 亚群都能有效地诱导 Foxp3(+)Treg 细胞。相比之下，只有 CD11c(+)CD11b(+)CD103(+)DC 能有效地诱导 Th17 细胞。与此一致的是，CD11c(+)CD11b(+)CD103(+)DC 的区域分布与 Th17 细胞的分布相关，十二指肠＞空肠＞回肠＞结肠。相反，CD11c(+)CD11b(-)CD103(+)DC、巨噬细胞和 Foxp3(+)Treg 细胞在结肠中最为丰富，在十二指肠中则很少。然而，重要的是，DC 和巨噬细胞亚群诱导 Foxp3(+)Treg 细胞与 Th17 细胞的能力强烈依赖于小鼠品系的来源。因此，来自 Charles River Laboratories 的 C57BL/6 小鼠的 DC（具有分段丝状菌，可原位诱导强烈的 Th17 细胞）比来自 The Jackson Laboratory 的 B6 小鼠的 DC 更有效地诱导 Th17 细胞，而诱导 Foxp3(+)Treg 细胞的效率较低。因此，肠道 APC 亚群的功能特化依赖于 T 细胞/APC 比例、区域定位和小鼠品系的来源。
