Exosomal let-7b-5p derived from Aspergillus fumigatus-treated human corneal epithelial cells promotes M1 macrophage activation via targeting SOCS-1
PurposeThis study aimed to explore the impact of exosomal miRNAs derived from Aspergillus fumigatus (A. fumigatus)-treated human corneal epithelial cells (HCECs) on M1 macrophage activation. We further clarified the mechanisms contributing to M1 macrophage activation in fungal keratitis.MethodsExoso...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1548802/full |
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| author | Xiaoming Yu Xiaoming Yu Xinyi Wu |
| author_facet | Xiaoming Yu Xiaoming Yu Xinyi Wu |
| author_sort | Xiaoming Yu |
| collection | DOAJ |
| description | PurposeThis study aimed to explore the impact of exosomal miRNAs derived from Aspergillus fumigatus (A. fumigatus)-treated human corneal epithelial cells (HCECs) on M1 macrophage activation. We further clarified the mechanisms contributing to M1 macrophage activation in fungal keratitis.MethodsExosomes were harvested from A. fumigatus-treated HCECs. Transmission electron microscopy, particle size analysis, and western blotting were performed to identify exosomes from HCECs. A laser confocal microscope was used to trace the exosomes. Macrophages were incubated with exosomes derived from A. fumigatus-treated HCECs. Global miRNA expression profiling of exosomes was assessed by high-throughput differential gene expression analysis. PCR and western blotting were used to detect the expression of M1-related proteins and SOCS-1. PCR was performed to detect the expression of pro-inflammatory cytokines and let-7b-5p. A dual-luciferase reporter assay was used to confirm the direct targeting of let-7b-5p.ResultsA. fumigatus-treated HCEC-derived exosomes notably promoted M1 macrophage activation and the production of inflammatory cytokines. Let-7b-5p was overexpressed in exosomes. Let-7b-5p inhibitors suppressed the M1 immune response induced by exosomes. Overexpression of let-7b-5p repressed the expression of SOCS-1, whereas the let-7b-5p inhibitor dramatically increased the expression of SOCS-1. Moreover, a dual-luciferase reporter assay confirmed that SOCS-1 is a direct target of let-7b-5p.ConclusionsLet-7b-5p is secreted by A. fumigatus-treated HCECs and transferred to macrophages via exosome secretion. The communication between A. fumigatus-treated HCECs and macrophages was facilitated by exosomal let-7b-5p, resulting in the activation of M1 macrophages. The exosome/let-7b-5p/SOCS-1 axis is vital for innate immunity against fungal keratitis and provides insights into the molecular mechanisms involved in this condition. |
| format | Article |
| id | doaj-art-c5f2911872f840fb910773f2c76d71ec |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-c5f2911872f840fb910773f2c76d71ec2025-08-20T03:02:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15488021548802Exosomal let-7b-5p derived from Aspergillus fumigatus-treated human corneal epithelial cells promotes M1 macrophage activation via targeting SOCS-1Xiaoming Yu0Xiaoming Yu1Xinyi Wu2Department of Ophthalmology, Qilu Hospital of Shandong University, No.107, Wenhua Xilu, Jinan, Shandong, ChinaDepartment of Ophthalmology, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Ophthalmology, Qilu Hospital of Shandong University, No.107, Wenhua Xilu, Jinan, Shandong, ChinaPurposeThis study aimed to explore the impact of exosomal miRNAs derived from Aspergillus fumigatus (A. fumigatus)-treated human corneal epithelial cells (HCECs) on M1 macrophage activation. We further clarified the mechanisms contributing to M1 macrophage activation in fungal keratitis.MethodsExosomes were harvested from A. fumigatus-treated HCECs. Transmission electron microscopy, particle size analysis, and western blotting were performed to identify exosomes from HCECs. A laser confocal microscope was used to trace the exosomes. Macrophages were incubated with exosomes derived from A. fumigatus-treated HCECs. Global miRNA expression profiling of exosomes was assessed by high-throughput differential gene expression analysis. PCR and western blotting were used to detect the expression of M1-related proteins and SOCS-1. PCR was performed to detect the expression of pro-inflammatory cytokines and let-7b-5p. A dual-luciferase reporter assay was used to confirm the direct targeting of let-7b-5p.ResultsA. fumigatus-treated HCEC-derived exosomes notably promoted M1 macrophage activation and the production of inflammatory cytokines. Let-7b-5p was overexpressed in exosomes. Let-7b-5p inhibitors suppressed the M1 immune response induced by exosomes. Overexpression of let-7b-5p repressed the expression of SOCS-1, whereas the let-7b-5p inhibitor dramatically increased the expression of SOCS-1. Moreover, a dual-luciferase reporter assay confirmed that SOCS-1 is a direct target of let-7b-5p.ConclusionsLet-7b-5p is secreted by A. fumigatus-treated HCECs and transferred to macrophages via exosome secretion. The communication between A. fumigatus-treated HCECs and macrophages was facilitated by exosomal let-7b-5p, resulting in the activation of M1 macrophages. The exosome/let-7b-5p/SOCS-1 axis is vital for innate immunity against fungal keratitis and provides insights into the molecular mechanisms involved in this condition.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1548802/fullfungal keratitisexosomeslet-7b-5pSOCS-1M1 macrophage activation |
| spellingShingle | Xiaoming Yu Xiaoming Yu Xinyi Wu Exosomal let-7b-5p derived from Aspergillus fumigatus-treated human corneal epithelial cells promotes M1 macrophage activation via targeting SOCS-1 Frontiers in Immunology fungal keratitis exosomes let-7b-5p SOCS-1 M1 macrophage activation |
| title | Exosomal let-7b-5p derived from Aspergillus fumigatus-treated human corneal epithelial cells promotes M1 macrophage activation via targeting SOCS-1 |
| title_full | Exosomal let-7b-5p derived from Aspergillus fumigatus-treated human corneal epithelial cells promotes M1 macrophage activation via targeting SOCS-1 |
| title_fullStr | Exosomal let-7b-5p derived from Aspergillus fumigatus-treated human corneal epithelial cells promotes M1 macrophage activation via targeting SOCS-1 |
| title_full_unstemmed | Exosomal let-7b-5p derived from Aspergillus fumigatus-treated human corneal epithelial cells promotes M1 macrophage activation via targeting SOCS-1 |
| title_short | Exosomal let-7b-5p derived from Aspergillus fumigatus-treated human corneal epithelial cells promotes M1 macrophage activation via targeting SOCS-1 |
| title_sort | exosomal let 7b 5p derived from aspergillus fumigatus treated human corneal epithelial cells promotes m1 macrophage activation via targeting socs 1 |
| topic | fungal keratitis exosomes let-7b-5p SOCS-1 M1 macrophage activation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1548802/full |
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