Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells.

Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells.
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DOI:
10.1016/j.immuni.2010.11.023
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发表时间:
2010-12-14
期刊:
影响因子:
32.4
通讯作者:
Reizis B
Reizis B
中科院分区:
医学1区
文献类型:
--
作者:
Ghosh HS;Cisse B;Bunin A;Lewis KL;Reizis B

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产生干扰素的浆细胞样树突状细胞(pDCs)与抗原呈递的经典树突状细胞(cdc)具有共同的祖细胞,但它们具有与淋巴细胞相似的独特形态和分子特征。目前尚不清楚pDCs独特的细胞命运是否在稳定状态下被积极维持。我们报道了成熟外周pDCs中转录因子E2-2的缺失导致它们自发分化为具有cDC特性的细胞。这包括pDC标记物的丢失,MHC II类表达和T细胞启动能力的增加,树突形态的获得和cDC特征基因的诱导。全基因组染色质免疫沉淀显示E2-2直接结合关键的pdc特异性和淋巴样基因,以及某些在cdc中富集的基因。因此,E2-2积极地维持成熟pDCs的细胞命运,并反对“默认”的cDC命运,部分通过直接调节谱系特异性基因表达程序。
The interferon-producing plasmacytoid dendritic cells (pDCs) share common progenitors with antigen-presenting classical dendritic cells (cDCs), yet they possess distinct morphology and molecular features resembling those of lymphocytes. It is unclear whether the unique cell fate of pDCs is actively maintained in the steady state. We report that the deletion of transcription factor E2-2 from mature peripheral pDCs caused their spontaneous differentiation into cells with cDC properties. This included the loss of pDC markers, increase in MHC class II expression and T cell priming capacity, acquisition of dendritic morphology and induction of cDC signature genes. Genome-wide chromatin immunoprecipitation revealed direct binding of E2-2 to key pDC-specific and lymphoid genes, as well as to certain genes enriched in cDCs. Thus, E2-2 actively maintains the cell fate of mature pDCs and opposes the “default” cDC fate, in part through direct regulation of lineage-specific gene expression programs.
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