Macrophagic Ym1 orchestrates γδT cell-derived IL-17 production and keratinocyte functionality to mediate psoriasis-like skin inflammation
Abstract Psoriasis is a chronic inflammatory skin disease, with the IL-17 pathway being a key contributor. Ym1, a positionally cloned inflammation regulatory gene linked to various disorders, has an unclear effect on skin inflammation. In this study, the role of Ym1 was investigated in both mannan a...
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Nature Portfolio
2025-08-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08628-1 |
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| author | Wentao Zhang Fei Li Yu Wang Meiyang Fan Yan Zhao Yanglong Guan Yan Zhou Shemin Lu Rikard Holmdahl Liesu Meng Wenhua Zhu |
| author_facet | Wentao Zhang Fei Li Yu Wang Meiyang Fan Yan Zhao Yanglong Guan Yan Zhou Shemin Lu Rikard Holmdahl Liesu Meng Wenhua Zhu |
| author_sort | Wentao Zhang |
| collection | DOAJ |
| description | Abstract Psoriasis is a chronic inflammatory skin disease, with the IL-17 pathway being a key contributor. Ym1, a positionally cloned inflammation regulatory gene linked to various disorders, has an unclear effect on skin inflammation. In this study, the role of Ym1 was investigated in both mannan and imiquimod-induced psoriasis-like dermatitis models, using Ym1-deficient congenic mice. Natural polymorphism of Ym1 influenced the development of skin inflammation, dependent on macrophages, since adoptive transferring of Ym1-deficient macrophages alleviated disease, whereas recombinant Ym1 worsened it. Particularly, Ym1 congenic mice exhibited decreased IL-17 production in innate immune cells, and depletion of γδT cells mitigated disease and lowered skin IL-17 levels. Additionally, RNA-seq analysis revealed Ym1-regulated keratinization in lesional skin. Recombination Ym1 directly influenced the inflammatory response and proliferation of mouse primary keratinocytes. Collectively, we conclude that Ym1 regulates γδT cell-derived IL-17 production and keratinocyte functionality, and thereby contributes to skin inflammation in mice. |
| format | Article |
| id | doaj-art-e7797c5c01d3453b8eb96b98eb8e9fd0 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| series | Communications Biology |
| spelling | doaj-art-e7797c5c01d3453b8eb96b98eb8e9fd02025-08-20T04:03:07ZengNature PortfolioCommunications Biology2399-36422025-08-018111210.1038/s42003-025-08628-1Macrophagic Ym1 orchestrates γδT cell-derived IL-17 production and keratinocyte functionality to mediate psoriasis-like skin inflammationWentao Zhang0Fei Li1Yu Wang2Meiyang Fan3Yan Zhao4Yanglong Guan5Yan Zhou6Shemin Lu7Rikard Holmdahl8Liesu Meng9Wenhua Zhu10National-local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong UniversityInstitute of Molecular and Translational Medicine (IMTM), and Department of Biochemistry and Molecular Biology, Xi’an Jiaotong University Health Science CenterInstitute of Molecular and Translational Medicine (IMTM), and Department of Biochemistry and Molecular Biology, Xi’an Jiaotong University Health Science CenterDepartment of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong UniversityInstitute of Molecular and Translational Medicine (IMTM), and Department of Biochemistry and Molecular Biology, Xi’an Jiaotong University Health Science CenterDepartment of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong UniversityNational-local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong UniversityNational-local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong UniversityNational-local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong UniversityNational-local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Psoriasis is a chronic inflammatory skin disease, with the IL-17 pathway being a key contributor. Ym1, a positionally cloned inflammation regulatory gene linked to various disorders, has an unclear effect on skin inflammation. In this study, the role of Ym1 was investigated in both mannan and imiquimod-induced psoriasis-like dermatitis models, using Ym1-deficient congenic mice. Natural polymorphism of Ym1 influenced the development of skin inflammation, dependent on macrophages, since adoptive transferring of Ym1-deficient macrophages alleviated disease, whereas recombinant Ym1 worsened it. Particularly, Ym1 congenic mice exhibited decreased IL-17 production in innate immune cells, and depletion of γδT cells mitigated disease and lowered skin IL-17 levels. Additionally, RNA-seq analysis revealed Ym1-regulated keratinization in lesional skin. Recombination Ym1 directly influenced the inflammatory response and proliferation of mouse primary keratinocytes. Collectively, we conclude that Ym1 regulates γδT cell-derived IL-17 production and keratinocyte functionality, and thereby contributes to skin inflammation in mice.https://doi.org/10.1038/s42003-025-08628-1 |
| spellingShingle | Wentao Zhang Fei Li Yu Wang Meiyang Fan Yan Zhao Yanglong Guan Yan Zhou Shemin Lu Rikard Holmdahl Liesu Meng Wenhua Zhu Macrophagic Ym1 orchestrates γδT cell-derived IL-17 production and keratinocyte functionality to mediate psoriasis-like skin inflammation Communications Biology |
| title | Macrophagic Ym1 orchestrates γδT cell-derived IL-17 production and keratinocyte functionality to mediate psoriasis-like skin inflammation |
| title_full | Macrophagic Ym1 orchestrates γδT cell-derived IL-17 production and keratinocyte functionality to mediate psoriasis-like skin inflammation |
| title_fullStr | Macrophagic Ym1 orchestrates γδT cell-derived IL-17 production and keratinocyte functionality to mediate psoriasis-like skin inflammation |
| title_full_unstemmed | Macrophagic Ym1 orchestrates γδT cell-derived IL-17 production and keratinocyte functionality to mediate psoriasis-like skin inflammation |
| title_short | Macrophagic Ym1 orchestrates γδT cell-derived IL-17 production and keratinocyte functionality to mediate psoriasis-like skin inflammation |
| title_sort | macrophagic ym1 orchestrates γδt cell derived il 17 production and keratinocyte functionality to mediate psoriasis like skin inflammation |
| url | https://doi.org/10.1038/s42003-025-08628-1 |
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