Yin Xiangyun, Yu Haisheng, Jin Xiaoyang, Li Jingyun, Guo Hao, Shi Quanxing, Yin Zhao, Xu Yong, Wang Xuefei, Liu Rong, Wang Shouli, Zhang Liguo
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100080, China.
J Immunol. 2017 Feb 15;198(4):1553-1564. doi: 10.4049/jimmunol.1600193. Epub 2017 Jan 13.
There are three major dendritic cell (DC) subsets in both humans and mice, that is, plasmacytoid DCs and two types of conventional DCs (cDCs), cDC1s and cDC2s. cDC2s are important for polarizing CD4 naive T cells into different subsets, including Th1, Th2, Th17, Th22, and regulatory T cells. In mice, cDC2s can be further divided into phenotypically and functionally distinct subgroups. However, subsets of human cDC2s have not been reported. In the present study, we showed that human blood CD1c cDCs (cDC2s) can be further separated into two subpopulations according to their CD5 expression status. Comparative transcriptome analyses showed that the CD5 DCs expressed higher levels of cDC2-specific genes, including IFN regulatory factor 4, which is essential for the cDC2 development and its migration to lymph nodes. In contrast, CD5 DCs preferentially expressed monocyte-related genes, including the lineage-specific transcription factor MAFB. Furthermore, compared with the CD5 subpopulation, the CD5 subpopulation showed stronger migration toward CCL21 and overrepresentation among migratory DCs in lymph nodes. Additionally, the CD5 DCs induced naive T cell proliferation more potently than did the CD5 DCs. Moreover, CD5 DCs induced higher levels of IL-10-, IL-22-, and IL-4-producing T cell formation, whereas CD5 DCs induced higher levels of IFN-γ-producing T cell formation. Thus, we show that human blood CD1c cDC2s encompass two subsets that differ significantly in phenotype, that is, gene expression and functions. We propose that these two subsets of human cDC2s could potentially play contrasting roles in immunity or tolerance.
在人类和小鼠中都存在三种主要的树突状细胞（DC）亚群，即浆细胞样DC和两种常规DC（cDC），cDC1和cDC2。cDC2对于将初始CD4 T细胞极化为不同亚群很重要，包括Th1、Th2、Th17、Th22和调节性T细胞。在小鼠中，cDC2可进一步分为表型和功能上不同的亚组。然而，人类cDC2的亚群尚未见报道。在本研究中，我们发现人类血液中的CD1c cDC（cDC2）可根据其CD5表达状态进一步分为两个亚群。比较转录组分析表明，CD5 DC表达更高水平的cDC2特异性基因，包括干扰素调节因子4，这对cDC2的发育及其向淋巴结的迁移至关重要。相比之下，CD5 DC优先表达单核细胞相关基因，包括谱系特异性转录因子MAFB。此外，与CD5亚群相比，CD5亚群对CCL21的迁移能力更强，且在淋巴结迁移性DC中占比更高。另外，CD5 DC比CD5 DC更有效地诱导初始T细胞增殖。而且，CD5 DC诱导产生IL-10、IL-22和IL-4的T细胞形成水平更高，而CD5 DC诱导产生IFN-γ的T细胞形成水平更高。因此，我们表明人类血液中的CD1c cDC2包含两个在表型上有显著差异的亚群，即基因表达和功能。我们提出，人类cDC2的这两个亚群可能在免疫或耐受中发挥相反的作用。
