New insights into the basic biology of acute graft-versus-host-disease.
New insights into the basic biology of acute graft-versus-host-disease.
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DOI：
10.3324/haematol.2019.240291
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发表时间：
2020-11-01
期刊：
影响因子：
10.1
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li A;Abraham C;Wang Y;Zhang Y
尽管异基因造血干细胞移植是许多血液和非血液疾病的重要治疗方法，但急性移植物抗宿主病（aGvHD）是其成功的主要障碍。aGvHD的发病机制分为三个不同的阶段，其主要是由于输注的供体T细胞与造血和非造血来源的许多细胞类型之间的相互作用而发生的。鉴于该疾病极其复杂的生物学，表观遗传学已成为检查aGvHD的框架。本综述重点关注新发现，阐明特定表观遗传调节因子在T细胞介导的aGvHD发展中所发挥的作用，并讨论它们的调节如何破坏该过程并产生有益影响。DNA甲基转移酶、组蛋白甲基转移酶和组蛋白脱乙酰基酶是跨aGvHD引发、诱导和效应物阶段最密切研究的调节剂，并且已经在鼠模型和临床试验中使用药物和其他方法操纵，具有不同程度的成功。抗原呈递细胞、效应T细胞和记忆T细胞等以不同的方式被这些调节剂靶向和影响。最后，我们的评论强调了新的研究方向和潜在的新的目标调制废除aGvHD。
Although allogeneic hematopoietic stem cell transplantation is an important therapy for many hematologic and non-hematologic diseases, acute graft-versus-host disease (aGvHD) is a major obstacle to its success. The pathogenesis of aGvHD is divided into three distinct phases which occur largely as the result of interactions between infused donor T cells and numerous cell types of both hematopoietic and non-hematopoietic origin. In light of the disease’s immensely complex biology, epigenetics has emerged as a framework with which to examine aGvHD. This review focuses on new findings that clarify the roles that specific epigenetic regulators play in T-cell-mediated aGvHD development and discusses how their modulation could disrupt that process with beneficial effects. DNA methyltransferases, histone methyltransferases and histone deacetylases are the most closely studied regulators across aGvHD priming, induction and effector phases and have been manipulated using drugs and other methods in both murine models and clinical trials, with varying degrees of success. Antigen-presenting cells, effector T cells and memory T cells, among others, are targeted and affected by these regulators in different ways. Finally, our review highlights new directions for study and potential novel targets for modulation to abrogate aGvHD.
影响因子：
4.3
作者：
Kato, Koji;Cui, Shuaiying;Kuick, Rork;Mineishi, Shin;Hexner, Elizabeth;Ferrara, James L. M.;Emerson, Stephen G.;Zhang, Yi
通讯作者：
Zhang, Yi