Dynamic expression of BCL6 in murine conventional dendritic cells during in vivo development and activation.

Dynamic expression of BCL6 in murine conventional dendritic cells during in vivo development and activation.
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DOI:
10.1371/journal.pone.0101208
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Haberman AM
Haberman AM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang TT;Liu D;Calabro S;Eisenbarth SC;Cattoretti G;Haberman AM

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转录抑制因子BCL6在生发中心B细胞和滤泡辅助性T细胞的发育中起重要作用。然而,对bcl6在其他细胞类型中的表达和功能知之甚少。在小鼠树突状细胞(DC)的体内个体发育过程中,BCL6在骨髓造血干细胞、普通DC前体和常规DC的受控前体(前CDCs)中不表达,但在外周血前CDCs中表达升高。在次级淋巴器官中,随着前CDC分化为CDC,Bcl6蛋白水平升高。CD8+CDC亚群中α+CDC的表达水平最高。Ki-67联合染色显示BCL6hi CDCs比BCL6lo CDCs具有更强的增殖能力。佐剂接种后CD11cint MHC IIi CD86细胞的BCL6水平显著降低。激活诱导的bcl6减少与细胞增殖减少相关。脂多糖注射研究进一步证实,在CD11cint MHC III类CDC成熟过程中,BCL6水平受微生物刺激的动态调节。在MYD88−/−TRIF−/−小鼠注射脂多糖后,CDC中bcl6水平的这种下降没有发生。因此,小鼠CDCs在体内发育、成熟和激活过程中对Bcl6蛋白水平的调节是动态的。
The transcriptional repressor BCL6 plays an essential role in the development of germinal center B cells and follicular helper T cells. However, much less is known about the expression and function of BCL6 in other cell types. Here we report that during murine dendritic cell (DC) ontogeny in vivo, BCL6 is not expressed in bone marrow hematopoietic stem cells, common DC precursors and committed precursors of conventional DCs (pre-cDCs), but is elevated in peripheral pre-cDCs. BCL6 protein levels rise as pre-cDCs differentiate into cDCs in secondary lymphoid organs. Elevated protein levels of Bcl6 are observed in all cDC subsets, with CD8α+ cDCs displaying the greatest levels. Co-staining of Ki-67 revealed BCL6hi cDCs to be more proliferative than BCL6lo cDCs. After adjuvant inoculation, BCL6 levels are significantly reduced in the CD11cint MHC class IIhi CD86hi cDCs. Activation-induced BCL6 reduction correlated with reduced proliferation. A LPS injection study further confirmed that, in response to microbial stimuli, BCL6 levels are dynamically regulated during the maturation of CD11cint MHC class IIhi splenic cDCs. This reduction of BCL6 levels in cDCs does not occur after LPS injection in MyD88−/− TRIF−/− mice. Thus, regulation of Bcl6 protein levels is dynamic in murine cDCs during development, maturation and activation in vivo.
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