Keratinocyte SR-B1 expression and targeting in cytokine-driven skin inflammation
Abstract Background Strategies to treat inflammatory skin conditions require identifying new targets involved in interactions between overlying epithelial and underlying dermal immune cells. Scavenger receptor class B type 1 (SR-B1) is a cell surface receptor that binds high-density lipoproteins (HD...
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Nature Portfolio
2025-04-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00804-y |
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| author | Jacquelyn Trujillo Andrea E. Calvert Jonathan S. Rink Bethany E. Perez White Fabiola Sepulveda Dauren Biyashev Kurt Q. Lu Robert M. Lavker Han Peng C. Shad Thaxton |
| author_facet | Jacquelyn Trujillo Andrea E. Calvert Jonathan S. Rink Bethany E. Perez White Fabiola Sepulveda Dauren Biyashev Kurt Q. Lu Robert M. Lavker Han Peng C. Shad Thaxton |
| author_sort | Jacquelyn Trujillo |
| collection | DOAJ |
| description | Abstract Background Strategies to treat inflammatory skin conditions require identifying new targets involved in interactions between overlying epithelial and underlying dermal immune cells. Scavenger receptor class B type 1 (SR-B1) is a cell surface receptor that binds high-density lipoproteins (HDL) and mediates inflammatory responses in immune and endothelial cells. The SR-B1 receptor is also expressed in keratinocytes, but its role in inflammatory skin diseases remains unexplored. Methods To investigate keratinocyte SR-B1 in the setting of inflammation, we measured its expression in skin biopsy samples obtained from patients with psoriasis; human skin explants exposed to the inflammatory cytokine, interleukin-17A (IL-17A); and mouse skin exposed to the pro-inflammatory agent, imiquimod (IMQ). We also evaluated the effects of SR-B1 knockdown on primary keratinocyte responses to IL-17A. Finally, we employed a synthetic HDL-nanoparticle (HDL NP) to investigate the therapeutic potential of targeting SR-B1 in IL-17A-stimulated keratinocytes and in male C57BL/6 mice with IMQ-induced skin inflammation. Results Our data show SR-B1 expression is increased in diseased human skin and in both human and mouse models of skin inflammation. SR-B1 knockdown in keratinocytes exacerbates the inflammatory response to IL-17A, whereas targeting SR-B1 with HDL NP attenuates this response. In the IMQ murine model, topical application of HDL NPs improves the skin phenotype, normalizes SR-B1 expression, and reduces molecular and cellular markers of inflammation. Conclusions Overall, SR-B1 plays a role in skin inflammation and HDL NP-mediated targeting of SR-B1 in keratinocytes may offer a targeted new therapy for inflammatory skin disease. |
| format | Article |
| id | doaj-art-14e2ba4e02144aac99c3238ea0e81604 |
| institution | OA Journals |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-14e2ba4e02144aac99c3238ea0e816042025-08-20T02:25:41ZengNature PortfolioCommunications Medicine2730-664X2025-04-015111310.1038/s43856-025-00804-yKeratinocyte SR-B1 expression and targeting in cytokine-driven skin inflammationJacquelyn Trujillo0Andrea E. Calvert1Jonathan S. Rink2Bethany E. Perez White3Fabiola Sepulveda4Dauren Biyashev5Kurt Q. Lu6Robert M. Lavker7Han Peng8C. Shad Thaxton9Department of Urology, Northwestern University Feinberg School of MedicineDepartment of Urology, Northwestern University Feinberg School of MedicineDepartment of Urology, Northwestern University Feinberg School of MedicineDepartment of Dermatology, Northwestern University Feinberg School of MedicineDepartment of Dermatology, Northwestern University Feinberg School of MedicineDepartment of Dermatology, Northwestern University Feinberg School of MedicineDepartment of Dermatology, Northwestern University Feinberg School of MedicineDepartment of Dermatology, Northwestern University Feinberg School of MedicineDepartment of Dermatology, Northwestern University Feinberg School of MedicineDepartment of Urology, Northwestern University Feinberg School of MedicineAbstract Background Strategies to treat inflammatory skin conditions require identifying new targets involved in interactions between overlying epithelial and underlying dermal immune cells. Scavenger receptor class B type 1 (SR-B1) is a cell surface receptor that binds high-density lipoproteins (HDL) and mediates inflammatory responses in immune and endothelial cells. The SR-B1 receptor is also expressed in keratinocytes, but its role in inflammatory skin diseases remains unexplored. Methods To investigate keratinocyte SR-B1 in the setting of inflammation, we measured its expression in skin biopsy samples obtained from patients with psoriasis; human skin explants exposed to the inflammatory cytokine, interleukin-17A (IL-17A); and mouse skin exposed to the pro-inflammatory agent, imiquimod (IMQ). We also evaluated the effects of SR-B1 knockdown on primary keratinocyte responses to IL-17A. Finally, we employed a synthetic HDL-nanoparticle (HDL NP) to investigate the therapeutic potential of targeting SR-B1 in IL-17A-stimulated keratinocytes and in male C57BL/6 mice with IMQ-induced skin inflammation. Results Our data show SR-B1 expression is increased in diseased human skin and in both human and mouse models of skin inflammation. SR-B1 knockdown in keratinocytes exacerbates the inflammatory response to IL-17A, whereas targeting SR-B1 with HDL NP attenuates this response. In the IMQ murine model, topical application of HDL NPs improves the skin phenotype, normalizes SR-B1 expression, and reduces molecular and cellular markers of inflammation. Conclusions Overall, SR-B1 plays a role in skin inflammation and HDL NP-mediated targeting of SR-B1 in keratinocytes may offer a targeted new therapy for inflammatory skin disease.https://doi.org/10.1038/s43856-025-00804-y |
| spellingShingle | Jacquelyn Trujillo Andrea E. Calvert Jonathan S. Rink Bethany E. Perez White Fabiola Sepulveda Dauren Biyashev Kurt Q. Lu Robert M. Lavker Han Peng C. Shad Thaxton Keratinocyte SR-B1 expression and targeting in cytokine-driven skin inflammation Communications Medicine |
| title | Keratinocyte SR-B1 expression and targeting in cytokine-driven skin inflammation |
| title_full | Keratinocyte SR-B1 expression and targeting in cytokine-driven skin inflammation |
| title_fullStr | Keratinocyte SR-B1 expression and targeting in cytokine-driven skin inflammation |
| title_full_unstemmed | Keratinocyte SR-B1 expression and targeting in cytokine-driven skin inflammation |
| title_short | Keratinocyte SR-B1 expression and targeting in cytokine-driven skin inflammation |
| title_sort | keratinocyte sr b1 expression and targeting in cytokine driven skin inflammation |
| url | https://doi.org/10.1038/s43856-025-00804-y |
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