Id2 expression delineates differential checkpoints in the genetic program of CD8α+ and CD103+ dendritic cell lineages.

Id2 expression delineates differential checkpoints in the genetic program of CD8α+ and CD103+ dendritic cell lineages.
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DOI:
10.1038/emboj.2011.163
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发表时间:
2011-05-17
期刊:
影响因子:
11.4
通讯作者:
Belz, Gabrielle T.
Belz, Gabrielle T.
中科院分区:
生物学1区
文献类型:
--
作者:
Jackson, Jacob T.;Hu, Yifang;Liu, Ruijie;Masson, Frederick;D'Amico, Angela;Carotta, Sebastian;Xin, Annie;Camilleri, Mary J.;Mount, Adele M.;Kallies, Axel;Wu, Li;Smyth, Gordon K.;Nutt, Stephen L.;Belz, Gabrielle T.

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树突状细胞(dc)在诱导适应性免疫应答中起着关键作用。转录因子Id2, Batf3和Irf-8在小鼠DC分化的许多方面都是必需的,包括CD8α+和CD103+ DC的发育。它们是如何调节DC子集规范的还不完全清楚。使用Id2- gfp报告系统,我们发现Id2在所有cDC亚群中广泛表达,在CD103+和CD8α+谱系中表达最高。值得注意的是,CD103+ DC是唯一能够在体外构成交叉呈递细胞相关抗原的DC。Irf-8缺乏影响几乎所有常规dc (cdc)的发育丧失,而Batf3缺乏导致Sirp-α - dc的发育,从而损害存活。在分化过程中暴露于GM-CSF诱导Id2-GFP+ dc中CD103的表达。它不能恢复体外对Batf3−/−或CD103−Sirp-α−dc的交叉呈递能力。因此,在cdc的发展过程中,Irf-8和Batf3调控着DC分化的不同阶段。利用Id2-GFP定位DC亚群分化的遗传图谱可能对理解DC亚群在保护性和病理性免疫反应中的相互作用具有广泛的意义。
Dendritic cells (DCs) have critical roles in the induction of the adaptive immune response. The transcription factors Id2, Batf3 and Irf-8 are required for many aspects of murine DC differentiation including development of CD8α+ and CD103+ DCs. How they regulate DC subset specification is not completely understood. Using an Id2-GFP reporter system, we show that Id2 is broadly expressed in all cDC subsets with the highest expression in CD103+ and CD8α+ lineages. Notably, CD103+ DCs were the only DC able to constitutively cross-present cell-associated antigens in vitro. Irf-8 deficiency affected loss of development of virtually all conventional DCs (cDCs) while Batf3 deficiency resulted in the development of Sirp-α− DCs that had impaired survival. Exposure to GM-CSF during differentiation induced expression of CD103 in Id2-GFP+ DCs. It did not restore cross-presenting capacity to Batf3−/− or CD103−Sirp-α−DCs in vitro. Thus, Irf-8 and Batf3 regulate distinct stages in DC differentiation during the development of cDCs. Genetic mapping DC subset differentiation using Id2-GFP may have broad implications in understanding the interplay of DC subsets during protective and pathological immune responses.
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