{"_":"METTL7A依赖的mA甲基化协调CXCR4中性粒细胞致病性和皮肤炎症中的NETosis。","sup":["6","hi"]}
{"_":"METTL7A-Dependent mA Methylation Orchestrates CXCR4 Neutrophil Pathogenicity and NETosis in Skin Inflammation.","sup":["6","hi"]}
摘要(中文译文)
银屑病患者中C-X-C趋化因子受体4高表达（CXCR4）中性粒细胞释放的中性粒细胞胞外诱捕网（NETs）是皮肤炎症的主要贡献因素，然而调控NETosis的上游表观转录组学机制仍不明确。本研究探讨了甲基转移酶样蛋白7A（METTL7A）在N6-甲基腺苷（m6A）介导的中性粒细胞活化及银屑病发病机制中的作用。通过对银屑病患者CXCR4中性粒细胞进行转录组分析、m6A RNA免疫沉淀、体外功能实验及体内小鼠皮肤炎症模型，结合基因沉默和过继转移实验，我们证明METTL7A在致病性和衰老的CXCR4中性粒细胞中优先上调，并与疾病严重程度呈正相关。METTL7A表达在人早幼粒细胞白血病细胞（HL-60细胞）分化、成熟和活化过程中亦增加。沉默METTL7A可抑制中性粒细胞成熟和衰老，减少NETosis，并在体内减轻银屑病样炎症。过继转移METTL7A缺陷中性粒细胞进一步保护小鼠免受皮肤炎症。机制上，METTL7A通过m6A相关调控稳定磷脂爬行酶1（PLSCR1）mRNA，从而增强活性氧产生和中性粒细胞胞外诱捕网（NETs）形成。这些发现确定METTL7A是致病性CXCR4中性粒细胞的新型表观转录组调控因子，通过METTL7A-PLSCR1轴驱动NETosis和皮肤炎症，从而为开发针对中性粒细胞相关疾病的m6A靶向治疗提供了理论依据。
Abstract
Neutrophil extracellular traps (NETs) released by C-X-C motif chemokine receptor 4-high (CXCR4) neutrophils are major contributors to skin inflammation in psoriasis, yet the upstream epitranscriptomic mechanisms that regulate NETosis remain poorly defined. Here, we investigated the role of methyltransferase-like protein 7A (METTL7A) in -methyladenosine (mA)-mediated neutrophil activation and psoriasis pathogenesis. Using transcriptomic profiling of CXCR4 neutrophils from psoriasis patients, mA RNA immunoprecipitation, in vitro functional assays, and in vivo murine models of skin inflammation, along with genetic silencing and adoptive transfer experiments, we demonstrated that METTL7A was preferentially upregulated in pathogenic and aged CXCR4 neutrophils and was positively associated with disease severity. METTL7A expression also increased during human promyelocytic leukemia cells(HL-60 cell differentiation, maturation, and activation. Silencing inhibited neutrophil maturation and aging, reduced NETosis, and alleviated psoriasiform inflammation in vivo. Adoptive transfer of -deficient neutrophils further protected mice from skin inflammation. Mechanistically, METTL7A stabilized phospholipid scramblase 1 () mRNA through mA-associated regulation, thereby enhancing reactive oxygen species production and neutrophil extracellular traps (NETs) formation. These findings identify METTL7A as a novel epitranscriptomic regulator of pathogenic CXCR4 neutrophils, acting through the METTL7A-PLSCR1 axis to drive NETosis and skin inflammation, thereby providing a rationale for developing mA-targeted therapies in neutrophil-associated disorders.
如何引用
AMA
Wanting Liu, Jinkai Liang, Huiyi Quan, Xuan Liu, Kang Li, Xin Tang, et al. {"_":"METTL7A-Dependent mA Methylation Orchestrates CXCR4 Neutrophil Pathogenicity and NETosis in Skin Inflammation.","sup":["6","hi"]}. MedComm. 2026; doi:10.1002/mco2.70941.
APA
Wanting Liu, Jinkai Liang, Huiyi Quan, Xuan Liu, Kang Li, Xin Tang, et al (2026). {"_":"METTL7A-Dependent mA Methylation Orchestrates CXCR4 Neutrophil Pathogenicity and NETosis in Skin Inflammation.","sup":["6","hi"]}. MedComm. https://doi.org/10.1002/mco2.70941
GB/T 7714
Wanting Liu, Jinkai Liang, Huiyi Quan, Xuan Liu, Kang Li, Xin Tang, et al. {"_":"METTL7A-Dependent mA Methylation Orchestrates CXCR4 Neutrophil Pathogenicity and NETosis in Skin Inflammation.","sup":["6","hi"]}[J]. MedComm, 2026 doi:10.1002/mco2.70941.
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