Laboratory of Innate Immunity, National Institute of Immunology, New Delhi 110067, India;
J Immunol. 2013 Dec 15;191(12):5993-6001. doi: 10.4049/jimmunol.1203541. Epub 2013 Nov 13.
Dendritic cells (DCs) are heterogeneous cell populations represented by different subtypes, each varying in terms of gene expression patterns and specific functions. Recent studies identified transcription factors essential for the development of different DC subtypes, yet molecular mechanisms for the developmental program and functions remain poorly understood. In this study, we developed and characterized a mouse DC progenitor-like cell line, designated DC9, from Irf8(-/-) bone marrow cells as a model for DC development and function. Expression of Irf8 in DC9 cells led to plasmacytoid DCs and CD8α(+) DC-like cells, with a concomitant increase in plasmacytoid DC- and CD8α(+) DC-specific gene transcripts and induction of type I IFNs and IL12p40 following TLR ligand stimulation. Irf8 expression in DC9 cells led to an increase in Id2 and Batf3 transcript levels, transcription factors shown to be important for the development of CD8α(+) DCs. We show that, without Irf8, expression of Id2 and Batf3 was not sufficient for directing classical CD8α(+) DC development. When coexpressed with Irf8, Batf3 and Id2 had a synergistic effect on classical CD8α(+) DC development. We demonstrate that Irf8 is upstream of Batf3 and Id2 in the classical CD8α(+) DC developmental program and define the hierarchical relationship of transcription factors important for classical CD8α(+) DC development.
树突状细胞（DCs）是异质性细胞群体，由不同的亚型代表，每个亚型在基因表达模式和特定功能方面都有所不同。最近的研究确定了不同 DC 亚型发育所必需的转录因子，但对于发育程序和功能的分子机制仍知之甚少。在这项研究中，我们从 Irf8(-/-) 骨髓细胞中开发并表征了一种称为 DC9 的小鼠 DC 祖细胞样细胞系，作为 DC 发育和功能的模型。Irf8 在 DC9 细胞中的表达导致浆细胞样 DC 和 CD8α(+) DC 样细胞的产生，同时浆细胞样 DC 和 CD8α(+) DC 特异性基因转录物增加，并在 TLR 配体刺激后诱导 I 型 IFNs 和 IL12p40。Irf8 在 DC9 细胞中的表达导致 Id2 和 Batf3 转录物水平的增加，这两个转录因子被证明对 CD8α(+) DC 的发育很重要。我们表明，在没有 Irf8 的情况下，Id2 和 Batf3 的表达不足以指导经典的 CD8α(+) DC 发育。当与 Irf8 共表达时，Batf3 和 Id2 对经典的 CD8α(+) DC 发育具有协同作用。我们证明 Irf8 在经典的 CD8α(+) DC 发育程序中位于 Batf3 和 Id2 的上游，并确定了对经典的 CD8α(+) DC 发育很重要的转录因子的层次关系。
