H3K27me3 modulates trained immunity of monocytes in HDM-allergic diseases

• Published in: Frontiers in immunology Vol. 16; p. 1572796
• Main Authors: Han, Lingli, Li, Lin, Yao, Liangjiao, Bu, Huaqin, Tian, Yajie, Li, Qifan, Zhu, Ke, Yao, Haili, Wang, Xiaochuan, Qian, Maoxiang, Lu, Wei, Sun, Jinqiao
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.05.2025
• Subjects: Animals; Child; Disease Models, Animal; Epigenesis, Genetic; Female; H3K27me3; HDM; Histones - immunology; Histones - metabolism; Humans; Hypersensitivity - immunology; Immunity, Innate; Immunologic Memory; Immunology; inflammation; KDM6B; Male; Methylation; Mice; monocytes; Monocytes - immunology; Monocytes - metabolism; Pyroglyphidae - immunology; Trained Immunity; HDM; KDM6B; monocytes; inflammation; H3K27me3
• DOI: 10.3389/fimmu.2025.1572796
• ISSN: 1664-3224

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.