Zhang Deshuang, Xu Ting, Gao Xiaoxue, Qu Yi, Su Xiaojuan
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Front Immunol. 2025 Mar 24;16:1523503. doi: 10.3389/fimmu.2025.1523503. eCollection 2025.
Methyltransferase-like 3 (METTL3) plays a crucial role in post-transcriptional gene regulation. Substantial evidence links METTL3 to various immune dysfunctions, such as the suppression of antiviral immunity during viral infections and the disruption of immune tolerance in conditions like autoimmune diseases, myeloid leukemia, skin cancers, and anticancer immunotherapy. However, a thorough review and analysis of this evidence is currently missing, which limits the understanding of METTL3's mechanisms and significance in immune dysfunctions. This review aims to elucidate the roles and mechanisms of METTL3 in these immune issues, highlighting its connections and proposing new insights into its modulation of immune responses. Analysis results in this review suggest that METTL3 hampers antiviral immunity, worsens viral replication and infection, and disrupts immune tolerance; conversely, regulating METTL3 enhances antiviral immunity and facilitates viral clearance. Moreover, clinical data corroborates these findings, showing that METTL3 overexpression is associated with increased susceptibility to viral infections and autoimmune conditions. This review establishes a theoretical basis for considering METTL3 as a novel regulator, an important diagnostic biomarker, and a potential target for treating immune dysfunctions.
甲基转移酶样3（METTL3）在转录后基因调控中起着关键作用。大量证据表明METTL3与多种免疫功能障碍有关，如病毒感染期间抗病毒免疫的抑制以及自身免疫性疾病、髓系白血病、皮肤癌和抗癌免疫治疗等情况下免疫耐受的破坏。然而，目前缺乏对这些证据的全面综述和分析，这限制了对METTL3在免疫功能障碍中的机制和意义的理解。本综述旨在阐明METTL3在这些免疫问题中的作用和机制，强调其联系并提出对其调节免疫反应的新见解。本综述的分析结果表明，METTL3会阻碍抗病毒免疫，加剧病毒复制和感染，并破坏免疫耐受；相反，调节METTL3可增强抗病毒免疫并促进病毒清除。此外，临床数据证实了这些发现，表明METTL3过表达与病毒感染和自身免疫性疾病易感性增加有关。本综述为将METTL3视为一种新型调节剂、重要的诊断生物标志物和治疗免疫功能障碍的潜在靶点奠定了理论基础。
