H3K27me3 modulates trained immunity of monocytes in HDM-allergic diseases
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 coho...
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Frontiers Media S.A.
2025-05-01
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| author | Lingli Han Lingli Han Lin Li Liangjiao Yao Huaqin Bu Yajie Tian Qifan Li Ke Zhu Ke Zhu Haili Yao Xiaochuan Wang Maoxiang Qian Wei Lu Jinqiao Sun Jinqiao Sun |
| author_facet | Lingli Han Lingli Han Lin Li Liangjiao Yao Huaqin Bu Yajie Tian Qifan Li Ke Zhu Ke Zhu Haili Yao Xiaochuan Wang Maoxiang Qian Wei Lu Jinqiao Sun Jinqiao Sun |
| author_sort | Lingli Han |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e1b8106a3f12472bbc0c85d3e1be808b |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-e1b8106a3f12472bbc0c85d3e1be808b2025-08-20T03:05:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15727961572796H3K27me3 modulates trained immunity of monocytes in HDM-allergic diseasesLingli Han0Lingli Han1Lin Li2Liangjiao Yao3Huaqin Bu4Yajie Tian5Qifan Li6Ke Zhu7Ke Zhu8Haili Yao9Xiaochuan Wang10Maoxiang Qian11Wei Lu12Jinqiao Sun13Jinqiao Sun14Department of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaNational Health Commission (NHC) Key Laboratory of Neonatal Diseases, National Children's Medical Center, Shanghai, ChinaInstitute of Pediatrics and Department of Hematology and Oncology, Children’s Hospital of Fudan University, National Children’s Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-Laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaNational Health Commission (NHC) Key Laboratory of Neonatal Diseases, National Children's Medical Center, Shanghai, ChinaDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaInstitute of Pediatrics and Department of Hematology and Oncology, Children’s Hospital of Fudan University, National Children’s Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-Laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaNational Health Commission (NHC) Key Laboratory of Neonatal Diseases, National Children's Medical Center, Shanghai, ChinaBackgroundMonocytes 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1572796/fullHDMmonocytesinflammationKDM6BH3K27me3 |
| spellingShingle | Lingli Han Lingli Han Lin Li Liangjiao Yao Huaqin Bu Yajie Tian Qifan Li Ke Zhu Ke Zhu Haili Yao Xiaochuan Wang Maoxiang Qian Wei Lu Jinqiao Sun Jinqiao Sun H3K27me3 modulates trained immunity of monocytes in HDM-allergic diseases Frontiers in Immunology HDM monocytes inflammation KDM6B H3K27me3 |
| title | H3K27me3 modulates trained immunity of monocytes in HDM-allergic diseases |
| title_full | H3K27me3 modulates trained immunity of monocytes in HDM-allergic diseases |
| title_fullStr | H3K27me3 modulates trained immunity of monocytes in HDM-allergic diseases |
| title_full_unstemmed | H3K27me3 modulates trained immunity of monocytes in HDM-allergic diseases |
| title_short | H3K27me3 modulates trained immunity of monocytes in HDM-allergic diseases |
| title_sort | h3k27me3 modulates trained immunity of monocytes in hdm allergic diseases |
| topic | HDM monocytes inflammation KDM6B H3K27me3 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1572796/full |
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