PDF(Pubmed)
Abstract：
The immune system comprises a complex yet tightly regulated network of cells and molecules that play a critical role in protecting the body from infection and disease. The activity and development of each immune cell is regulated in a myriad of ways including through the cytokine milieu, the availability of key receptors, via tailored intracellular signalling cascades, dedicated transcription factors and even by directly modulating gene accessibility and expression; the latter is more commonly known as epigenetic regulation. In recent years, epigenetic regulators have begun to emerge as key players involved in modulating the immune system. Among these, the lysine methyltransferase DOT1L has gained significant attention for its involvement in orchestrating immune cell formation and function. In this review we provide an overview of the role of DOT1L across the immune system and the implications of this role on health and disease. We begin by elucidating the general mechanisms of DOT1L-mediated histone methylation and its impact on gene expression within immune cells. Subsequently, we provide a detailed and comprehensive overview of recent studies that identify DOT1L as a crucial regulator of immune cell development, differentiation, and activation. Next, we discuss the potential mechanisms of DOT1L-mediated regulation of immune cell function and shed light on how DOT1L might be contributing to immune cell homeostasis and dysfunction. We then provide food for thought by highlighting some of the current obstacles and technical limitations precluding a more in-depth elucidation of DOT1L\'s role. Finally, we explore the potential therapeutic implications of targeting DOT1L in the context of immune-related diseases and discuss ongoing research efforts to this end. Overall, this review consolidates the current paradigm regarding DOT1L\'s role across the immune network and emphasises its critical role in governing the healthy immune system and its potential as a novel therapeutic target for immune-related diseases. A deeper understanding of DOT1L\'s immunomodulatory functions could pave the way for innovative therapeutic approaches which fine-tune the immune response to enhance or restore human health.
摘要：
免疫系统包含一个复杂但受严格调节的细胞和分子网络，在保护身体免受感染和疾病中起着关键作用。每个免疫细胞的活性和发育以多种方式调节，包括通过细胞因子环境，关键受体的可用性，通过定制的细胞内信号级联，专门的转录因子，甚至通过直接调节基因的可及性和表达；后者更通常被称为表观遗传调控。近年来,表观遗传调节因子已经开始成为参与调节免疫系统的关键参与者。其中,赖氨酸甲基转移酶DOT1L因其参与协调免疫细胞的形成和功能而受到广泛关注。在这篇综述中，我们概述了DOT1L在免疫系统中的作用以及这种作用对健康和疾病的影响。我们首先阐明DOT1L介导的组蛋白甲基化的一般机制及其对免疫细胞内基因表达的影响。随后，我们提供了一个详细和全面的概述最近的研究，确定DOT1L作为免疫细胞发育的关键调节，分化,和激活。接下来,我们讨论了DOT1L介导的免疫细胞功能调节的潜在机制，并阐明了DOT1L如何促进免疫细胞稳态和功能障碍。然后，我们通过强调当前的一些障碍和技术限制来提供思考的食物，从而无法更深入地阐明DOT1L的作用。最后,我们探讨了在免疫相关疾病中靶向DOT1L的潜在治疗意义,并讨论了为此正在进行的研究工作.总的来说,这篇综述巩固了目前关于DOT1L在整个免疫网络中的作用的范式,并强调了其在控制健康免疫系统方面的关键作用及其作为免疫相关疾病新治疗靶点的潜力.对DOT1L免疫调节功能的更深入了解可以为创新的治疗方法铺平道路，这些方法可以微调免疫反应以增强或恢复人类健康。
