Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80+ liver-associated macrophages
Abstract Delivery of an mRNA formulated with lipid nanoparticles (LNPs) induces robust humoral and cell-mediated branches of the immune response. Depending on the LNP formula, mRNA encoding proteins can be detected in the liver upon intramuscular administration of mRNA/LNP in mice. This study invest...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-85234-5 |
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| author | Chitsuda Pongma Pornlapat Keawvilai Atsadang Boonmee Benjawan Wongprom Thitiporn Pattarakankul Chutamath Sittplangkoon Mohamad-Gabriel Alameh Patipark Kueanjinda James Heyes Kieu Lam Benjawan Saechue Kiat Ruxrungtham Tanapat Palaga |
| author_facet | Chitsuda Pongma Pornlapat Keawvilai Atsadang Boonmee Benjawan Wongprom Thitiporn Pattarakankul Chutamath Sittplangkoon Mohamad-Gabriel Alameh Patipark Kueanjinda James Heyes Kieu Lam Benjawan Saechue Kiat Ruxrungtham Tanapat Palaga |
| author_sort | Chitsuda Pongma |
| collection | DOAJ |
| description | Abstract Delivery of an mRNA formulated with lipid nanoparticles (LNPs) induces robust humoral and cell-mediated branches of the immune response. Depending on the LNP formula, mRNA encoding proteins can be detected in the liver upon intramuscular administration of mRNA/LNP in mice. This study investigated the impact of mRNA/LNP administration on liver-associated macrophages at the transcriptomic and epigenetic levels in a mouse model. An mRNA encoding ovalbumin (OVA) formulated with LNPs, was administered intramuscularly, and a robust OVA-specific antibody was detected in the serum on Day 7. F4/80+ liver-associated macrophages were isolated and subjected to RNA sequencing, which identified 554 genes whose expression levels were altered compared with those in the PBS control group. The expression of genes involved in macrophage inflammatory functions, such as Tnf, Il6 and Marco, were upregulated. Gene ontology enrichment analysis revealed that IL-6/JAK/STAT3 and TNFα/NF-κB hallmarks were significantly enriched, and mRNA/LNP-exposed liver-associated macrophages were characterized as M1-like cells based on the macrophage transcriptomic profiles. Enrichment of the active histone mark H3K4me3 showed that clusters of loci were highly increased in the mRNA/LNP group, indicating an impact of mRNA/LNPs on macrophage epigenetic profiles. The cis-regulatory regions of Tnf, Il6 and Marco showed enrichment of H3K4me3 marks, which correlated well with their increased transcription. Taken together, our data indicated that mRNA/LNP administration via the intramuscular route influences the gene expression and epigenetic profiles of liver-associated macrophages, reflecting its robust ability to induce an immune response. |
| format | Article |
| id | doaj-art-052974e026a84cecbc4a0df248108609 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-052974e026a84cecbc4a0df2481086092025-01-12T12:21:33ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-025-85234-5Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80+ liver-associated macrophagesChitsuda Pongma0Pornlapat Keawvilai1Atsadang Boonmee2Benjawan Wongprom3Thitiporn Pattarakankul4Chutamath Sittplangkoon5Mohamad-Gabriel Alameh6Patipark Kueanjinda7James Heyes8Kieu Lam9Benjawan Saechue10Kiat Ruxrungtham11Tanapat Palaga12Graduate Program in Biotechnology, Faculty of Science, Chulalongkorn UniversityGraduate Program in Biotechnology, Faculty of Science, Chulalongkorn UniversityDepartment of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Microbiology, Faculty of Science, Chulalongkorn UniversityDepartment of Microbiology, Faculty of Science, Chulalongkorn UniversityGraduate Program in Biotechnology, Faculty of Science, Chulalongkorn UniversityDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of MedicineDepartment of Microbiology, Faculty of Medicine, Chulalongkorn UniversityGenevant Sciences CorporationGenevant Sciences CorporationOne Health Research Unit, Faculty of Veterinary Science, Mahasarakham UniversityCenter of Excellence in Vaccine Research and Development (Chula Vaccine Research Center-Chula VRC), Faculty of Medicine, Chulalongkorn UniversityCenter of Excellence in Vaccine Research and Development (Chula Vaccine Research Center-Chula VRC), Faculty of Medicine, Chulalongkorn UniversityAbstract Delivery of an mRNA formulated with lipid nanoparticles (LNPs) induces robust humoral and cell-mediated branches of the immune response. Depending on the LNP formula, mRNA encoding proteins can be detected in the liver upon intramuscular administration of mRNA/LNP in mice. This study investigated the impact of mRNA/LNP administration on liver-associated macrophages at the transcriptomic and epigenetic levels in a mouse model. An mRNA encoding ovalbumin (OVA) formulated with LNPs, was administered intramuscularly, and a robust OVA-specific antibody was detected in the serum on Day 7. F4/80+ liver-associated macrophages were isolated and subjected to RNA sequencing, which identified 554 genes whose expression levels were altered compared with those in the PBS control group. The expression of genes involved in macrophage inflammatory functions, such as Tnf, Il6 and Marco, were upregulated. Gene ontology enrichment analysis revealed that IL-6/JAK/STAT3 and TNFα/NF-κB hallmarks were significantly enriched, and mRNA/LNP-exposed liver-associated macrophages were characterized as M1-like cells based on the macrophage transcriptomic profiles. Enrichment of the active histone mark H3K4me3 showed that clusters of loci were highly increased in the mRNA/LNP group, indicating an impact of mRNA/LNPs on macrophage epigenetic profiles. The cis-regulatory regions of Tnf, Il6 and Marco showed enrichment of H3K4me3 marks, which correlated well with their increased transcription. Taken together, our data indicated that mRNA/LNP administration via the intramuscular route influences the gene expression and epigenetic profiles of liver-associated macrophages, reflecting its robust ability to induce an immune response.https://doi.org/10.1038/s41598-025-85234-5mRNAImmunizationMacrophageLiverEpigenetics |
| spellingShingle | Chitsuda Pongma Pornlapat Keawvilai Atsadang Boonmee Benjawan Wongprom Thitiporn Pattarakankul Chutamath Sittplangkoon Mohamad-Gabriel Alameh Patipark Kueanjinda James Heyes Kieu Lam Benjawan Saechue Kiat Ruxrungtham Tanapat Palaga Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80+ liver-associated macrophages Scientific Reports mRNA Immunization Macrophage Liver Epigenetics |
| title | Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80+ liver-associated macrophages |
| title_full | Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80+ liver-associated macrophages |
| title_fullStr | Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80+ liver-associated macrophages |
| title_full_unstemmed | Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80+ liver-associated macrophages |
| title_short | Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80+ liver-associated macrophages |
| title_sort | effect of mrna formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of f4 80 liver associated macrophages |
| topic | mRNA Immunization Macrophage Liver Epigenetics |
| url | https://doi.org/10.1038/s41598-025-85234-5 |
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