CD8α+ DCs can be induced in the absence of transcription factors Id2, Nfil3, and Batf3
CD8α+ DCs can be induced in the absence of transcription factors Id2, Nfil3, and Batf3
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DOI：
10.1182/blood-2012-07-445650
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发表时间：
2013-02-28
期刊：
影响因子：
20.3
通讯作者：
Belz, Gabrielle T.
中科院分区：
文献类型：
--
作者：
Seillet, Cyril;Jackson, Jacob T.;Belz, Gabrielle T.
抗病毒免疫和交叉递呈是通过CD8α(+)和CD103(+)DC结构性地介导的。这些DC亚群的发展被认为需要转录因子IRF8、Id2、Nfil3和BATF3，尽管这个网络是如何调控的还不清楚。我们研究了在缺乏这些因素的情况下观察到的分化障碍的性质，发现尽管所有4个因素都是CD103(+)DC发育所必需的，但只有IRF8对CD8α(+)DC是必不可少的。在短期骨髓重建中，CD8α(+)DC在缺乏Id2、Nfil3和BATF3的情况下出现。这些“诱导的”CD8α(+)DC表现出经典CD8α(+)DC的几个特征，包括CD24、TLR3、Xcr1、Clec9A的表达，以及即使在没有BATF3的情况下也能交叉呈递可溶性的细胞相关抗原和病毒抗原的能力。总之，这些结果揭示了CD8α(+)DC独立于Id2、Nfil3和BATF3，但依赖于IRF8的一条先前未被描述的途径。
Antiviral immunity and cross-presentation is mediated constitutively through CD8 alpha(+) and CD103(+) DCs. Development of these DC subsets is thought to require the transcription factors Irf8, Id2, Nfil3, and Batf3, although how this network is regulated is poorly defined. We addressed the nature of the differentiation blocks observed in the absence of these factors and found that although all 4 factors are required for CD103(+) DC development, only Irf8 is essential for CD8 alpha(+) DCs. CD8 alpha(+) DCs emerged in the absence of Id2, Nfil3 and Batf3 in short-term bone marrow reconstitution. These "induced" CD8 alpha(+) DCs exhibit several hallmarks of classic CD8 alpha(+) DCs including the expression of CD24, Tlr3, Xcr1, Clec9A, and the capacity to cross-present soluble, cell-associated antigens and viral antigens even in the absence of Batf3. Collectively, these results uncover a previously undescribed pathway by which CD8 alpha(+) DCs emerge independent of Id2, Nfil3, and Batf3, but dependent on Irf8.