Chen Longmin, Zou Yuan, Dong Yan, Hong Tian, Xu Qianqian, Zhang Jing
Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430100, China.
Department of Rheumatology and Immunology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, China.
Genes Dis. 2025 Apr 3;12(6):101622. doi: 10.1016/j.gendis.2025.101622. eCollection 2025 Nov.
SET domain-containing 2 (SETD2) is a methyltransferase that catalyzes trimethylation of lysine 36 on H3 (H3K36me3) in mammals, an epigenetic mark associated with actively transcribed regions. SETD2 is implicated in multiple chromatin biological processes, such as alternative splicing, transcriptional regulation, DNA damage repair, and maintenance of genomic integrity. Extensive studies have demonstrated that -inactivating mutations and resultant dysregulation of these functions may result in tumorigenesis. However, the role of SETD2 in the development and function of immune cells receives relatively limited attention. In this review, we seek to summarize current knowledge of the biological function and underlying mechanisms of SETD2 and highlight its important role in immune cell biology. By influencing the biological processes of immune cells, SETD2 participates in the pathogenesis of immune-related diseases, including infection, cancers, autoimmune diseases, and inflammatory diseases. Finally, we discuss challenges and prospects for targeting SETD2 in immune cells to provide guidance for treating those diseases in clinical practice.
含SET结构域蛋白2（SETD2）是一种甲基转移酶，在哺乳动物中催化组蛋白H3赖氨酸36位点的三甲基化（H3K36me3），这是一种与活跃转录区域相关的表观遗传标记。SETD2参与多种染色质生物学过程，如可变剪接、转录调控、DNA损伤修复以及基因组完整性的维持。大量研究表明，这些功能的失活突变及由此导致的功能失调可能会引发肿瘤发生。然而，SETD2在免疫细胞发育和功能中的作用受到的关注相对较少。在本综述中，我们旨在总结目前关于SETD2生物学功能及潜在机制的认识，并强调其在免疫细胞生物学中的重要作用。通过影响免疫细胞的生物学过程，SETD2参与免疫相关疾病的发病机制，包括感染、癌症、自身免疫性疾病和炎症性疾病。最后，我们讨论了针对免疫细胞中SETD2的靶向治疗所面临的挑战和前景，为临床治疗这些疾病提供指导。
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