Epigenetic Regulation of Dendritic Cell Development and Function.
Epigenetic Regulation of Dendritic Cell Development and Function.
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DOI：
10.1097/ppo.0000000000000280
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Tian Y;Meng L;Zhang Y
免疫系统的特征在于产生结构和功能异质的免疫细胞，其构成复杂的先天性和适应性免疫。免疫细胞的这种异质性是由于基因表达的变化而不改变DNA序列。为了实现这种异质性，免疫细胞协调转录因子（TF）网络的表达和功能状态，其可以大致分为3类：促进造血细胞初始定型和分化的先锋TF，促进选定细胞谱系生成的亚群特异性TF，以及调节分化细胞中专门功能的免疫信号转导TF。已知表观遗传机制对于组织TF网络至关重要，从而控制免疫细胞谱系命运决定、可塑性和功能。表观遗传调节因子的作用可以在细胞有丝分裂期间遗传，主要通过基因位点处的DNA和组蛋白甲基化模式的修饰。通过这样做，免疫系统能够在移植环境中对刺激（例如病原体、肿瘤细胞、自身抗原或同种异体抗原）产生选择性但稳健的应答，同时保留保护宿主免受许多其他意外刺激所必需的免疫细胞库，并限制全身性炎症反应的有害作用。
The immune system is characterized by the generation of structurally and functionally heterogeneous immune cells that constitute complex innate and adaptive immunity. This heterogeneity of immune cells results from changes in the expression of genes without altering DNA sequence. To achieve this heterogeneity, immune cells orchestrate the expression and functional status of transcription factor (TF) networks, which can be broadly categorized into 3 classes: pioneer TFs that facilitate initial commitment and differentiation of hematopoietic cells, subset-specific TFs that promote the generation of selected cell lineages, and immune-signaling TFs that regulate specialized function in differentiated cells. Epigenetic mechanisms are known to be critical for organizing the TF networks, thereby controlling immune cell lineage-fate decisions, plasticity, and function. The effects of epigenetic regulators can be heritable during cell mitosis, primarily through the modification of DNA and histone methylation patterns at gene loci. By doing so, the immune system is enabled to mount a selective but robust response to stimuli, such as pathogens, tumor cells, autoantigens, or allogeneic antigens in the setting of transplantation, while preserving the immune cell reservoir necessary for protecting the host against numerous other unexpected stimuli and limit detrimental effect of systemic inflammatory reactions.