Targeting fibroblast TNF receptor 1 attenuates type 17 skin inflammation
Summary: Inflammation at epithelial barriers involves a complex cell communication network, with subsets of fibroblasts increasingly recognized as active players in immune cell recruitment. To investigate the role of fibroblasts in interleukin (IL)-17-mediated skin diseases, we analyzed single-cell...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725008824 |
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| author | Kellen J. Cavagnero Fengwu Li Carlos Aguilera Haley Jo Marta Palomo-Irigoyen Andrea Roso Mares Hung Chan Richard L. Gallo |
| author_facet | Kellen J. Cavagnero Fengwu Li Carlos Aguilera Haley Jo Marta Palomo-Irigoyen Andrea Roso Mares Hung Chan Richard L. Gallo |
| author_sort | Kellen J. Cavagnero |
| collection | DOAJ |
| description | Summary: Inflammation at epithelial barriers involves a complex cell communication network, with subsets of fibroblasts increasingly recognized as active players in immune cell recruitment. To investigate the role of fibroblasts in interleukin (IL)-17-mediated skin diseases, we analyzed single-cell transcriptomic data from human psoriatic skin and identified tumor necrosis factor (TNF) recognition by TNF receptor 1 (TNFR1) as the most upregulated pathway in immune-acting fibroblasts. Functionally, TNF induced TNFR1-dependent neutrophil chemokine expression in cultured fibroblasts. Transcriptomics of skin from patients treated with TNF inhibitors revealed that expression of fibroblast-derived neutrophil chemokines depends on TNF. To test the significance of TNF recognition by fibroblasts, we developed mice lacking TNFR1 specifically in fibroblasts that showed impaired neutrophil recruitment to the skin after intradermal IL-17A and TNF injection and topical imiquimod treatment. This study establishes TNF signaling in immune-acting fibroblasts as a key driver of type 17 skin inflammation, challenging the prevailing view that TNF acts predominantly through keratinocytes. |
| format | Article |
| id | doaj-art-37aed8e6e76747a9aa18e6a76599604c |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-37aed8e6e76747a9aa18e6a76599604c2025-08-20T03:36:35ZengElsevierCell Reports2211-12472025-08-0144811611110.1016/j.celrep.2025.116111Targeting fibroblast TNF receptor 1 attenuates type 17 skin inflammationKellen J. Cavagnero0Fengwu Li1Carlos Aguilera2Haley Jo3Marta Palomo-Irigoyen4Andrea Roso Mares5Hung Chan6Richard L. Gallo7Department of Dermatology, University of California, San Diego, La Jolla, CA 92093, USADepartment of Dermatology, University of California, San Diego, La Jolla, CA 92093, USADepartment of Dermatology, University of California, San Diego, La Jolla, CA 92093, USADepartment of Dermatology, University of California, San Diego, La Jolla, CA 92093, USADepartment of Dermatology, University of California, San Diego, La Jolla, CA 92093, USADepartment of Dermatology, University of California, San Diego, La Jolla, CA 92093, USADepartment of Dermatology, University of California, San Diego, La Jolla, CA 92093, USADepartment of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA; Corresponding authorSummary: Inflammation at epithelial barriers involves a complex cell communication network, with subsets of fibroblasts increasingly recognized as active players in immune cell recruitment. To investigate the role of fibroblasts in interleukin (IL)-17-mediated skin diseases, we analyzed single-cell transcriptomic data from human psoriatic skin and identified tumor necrosis factor (TNF) recognition by TNF receptor 1 (TNFR1) as the most upregulated pathway in immune-acting fibroblasts. Functionally, TNF induced TNFR1-dependent neutrophil chemokine expression in cultured fibroblasts. Transcriptomics of skin from patients treated with TNF inhibitors revealed that expression of fibroblast-derived neutrophil chemokines depends on TNF. To test the significance of TNF recognition by fibroblasts, we developed mice lacking TNFR1 specifically in fibroblasts that showed impaired neutrophil recruitment to the skin after intradermal IL-17A and TNF injection and topical imiquimod treatment. This study establishes TNF signaling in immune-acting fibroblasts as a key driver of type 17 skin inflammation, challenging the prevailing view that TNF acts predominantly through keratinocytes.http://www.sciencedirect.com/science/article/pii/S2211124725008824CP: Immunology |
| spellingShingle | Kellen J. Cavagnero Fengwu Li Carlos Aguilera Haley Jo Marta Palomo-Irigoyen Andrea Roso Mares Hung Chan Richard L. Gallo Targeting fibroblast TNF receptor 1 attenuates type 17 skin inflammation Cell Reports CP: Immunology |
| title | Targeting fibroblast TNF receptor 1 attenuates type 17 skin inflammation |
| title_full | Targeting fibroblast TNF receptor 1 attenuates type 17 skin inflammation |
| title_fullStr | Targeting fibroblast TNF receptor 1 attenuates type 17 skin inflammation |
| title_full_unstemmed | Targeting fibroblast TNF receptor 1 attenuates type 17 skin inflammation |
| title_short | Targeting fibroblast TNF receptor 1 attenuates type 17 skin inflammation |
| title_sort | targeting fibroblast tnf receptor 1 attenuates type 17 skin inflammation |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725008824 |
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