Han Lingli, Li Lin, Yao Liangjiao, Bu Huaqin, Tian Yajie, Li Qifan, Zhu Ke, Yao Haili, Wang Xiaochuan, Qian Maoxiang, Lu Wei, Sun Jinqiao
Department of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
National Health Commission (NHC) Key Laboratory of Neonatal Diseases, National Children's Medical Center, Shanghai, China.
Front Immunol. 2025 May 28;16:1572796. doi: 10.3389/fimmu.2025.1572796. eCollection 2025.
Monocytes have been confirmed to increase in persistently food-allergic children. A phenomenon of innate immune memory, called trained immunity, has also been observed in monocytes from allergic children. However, the underlying mechanism remains poorly understood.
We enrolled a cohort of HDM-allergic children alongside age-matched healthy controls and established an HDM-sensitized allergic mouse model. Flow cytometric analyses were conducted to quantify monocyte frequencies in clinical cohorts and experimental animals. We performed integrated transcriptomic profiling via RNA-seq combined with chromatin occupancy analysis using CUT&Tag technology in parallel human and murine samples to elucidate the molecular mechanisms.
In our study, we demonstrated a reduced H3K27me3 methylation level accompanied by an increased proportion and a proinflammatory transcriptional memory in monocytes from house dust mite (HDM)-allergic human subjects. The same transcriptional and epigenetic phenotype was also confirmed in HDM-sensitized mice. Finally, the administration of GSK-J4, which upregulates H3K27me3 level in murine monocytes, attenuated the inflammatory response and .
Our study confirms that H3K27me3 methylation modulates the trained immunity in monocytes and regulates HDM-allergic diseases through an inflammatory-dependent mechanism.
单核细胞在持续性食物过敏儿童中已被证实会增加。在过敏儿童的单核细胞中也观察到一种称为训练免疫的先天免疫记忆现象。然而，其潜在机制仍知之甚少。
我们招募了一组对屋尘螨（HDM）过敏的儿童以及年龄匹配的健康对照，并建立了HDM致敏的过敏性小鼠模型。进行流式细胞术分析以量化临床队列和实验动物中的单核细胞频率。我们通过RNA测序结合使用CUT&Tag技术的染色质占据分析，在平行的人类和小鼠样本中进行综合转录组分析，以阐明分子机制。
在我们的研究中，我们证明了在对屋尘螨（HDM）过敏的人类受试者的单核细胞中，H3K27me3甲基化水平降低，同时单核细胞比例增加且存在促炎转录记忆。在HDM致敏的小鼠中也证实了相同的转录和表观遗传表型。最后，给予上调小鼠单核细胞中H3K27me3水平的GSK-J4可减轻炎症反应。
我们的研究证实，H3K27me3甲基化调节单核细胞中的训练免疫，并通过炎症依赖机制调节HDM过敏性疾病。
