Table 1_H3K27me3 modulates trained immunity of monocytes in HDM-allergic diseases.docx

BackgroundMonocytes 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.
MethodsWe 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.
ResultsIn 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 in vitro and in vivo.
ConclusionsOur study confirms that H3K27me3 methylation modulates the trained immunity in monocytes and regulates HDM-allergic diseases through an inflammatory-dependent mechanism.

背景 单核细胞已被证实会在持续性食物过敏儿童体内水平升高。此前已有研究在过敏儿童的单核细胞中观察到一种被称为训练免疫（trained immunity）的先天免疫记忆现象，但其具体潜在机制仍未得到充分阐明。
方法 本研究纳入一组屋尘螨（house dust mite, HDM）过敏儿童，并设置年龄匹配的健康对照群体，同时构建屋尘螨致敏的过敏小鼠模型。通过流式细胞术分析，对临床队列与实验动物体内的单核细胞占比进行定量检测。本研究同步在人类与小鼠样本中，采用RNA测序（RNA-seq）开展整合转录组分析，并结合CUT&Tag技术进行染色质占据分析，以解析其潜在分子机制。
结果 本研究发现，屋尘螨过敏患者的单核细胞中，H3K27me3甲基化水平显著降低，同时单核细胞比例升高，并呈现促炎性转录记忆特征。这一转录组与表观遗传表型在屋尘螨致敏小鼠体内同样得到验证。最后，向小鼠单核细胞中施用可上调H3K27me3水平的GSK-J4，可在体外与体内实验中均减轻炎症反应。
结论 本研究证实，H3K27me3甲基化可调控单核细胞的训练免疫，并通过炎症依赖的机制参与屋尘螨过敏性疾病的发生发展。