Role of bulge epidermal stem cells and TSLP signaling in psoriasis
Abstract Psoriasis is a common inflammatory skin disease involving a cross‐talk between epidermal and immune cells. The role of specific epidermal stem cell populations, including hair follicle stem cells (HF‐SCs) in psoriasis is not well defined. Here, we show reduced expression of c‐JUN and JUNB i...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2019-11-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201910697 |
| _version_ | 1797288060771106816 |
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| author | Nuria Gago‐Lopez Liliana F Mellor Diego Megías Guillermo Martín‐Serrano Ander Izeta Francisco Jimenez Erwin F Wagner |
| author_facet | Nuria Gago‐Lopez Liliana F Mellor Diego Megías Guillermo Martín‐Serrano Ander Izeta Francisco Jimenez Erwin F Wagner |
| author_sort | Nuria Gago‐Lopez |
| collection | DOAJ |
| description | Abstract Psoriasis is a common inflammatory skin disease involving a cross‐talk between epidermal and immune cells. The role of specific epidermal stem cell populations, including hair follicle stem cells (HF‐SCs) in psoriasis is not well defined. Here, we show reduced expression of c‐JUN and JUNB in bulge HF‐SCs in patients with scalp psoriasis. Using lineage tracing in mouse models of skin inflammation with inducible deletion of c‐Jun and JunB, we found that mutant bulge HF‐SCs initiate epidermal hyperplasia and skin inflammation. Mechanistically, thymic stromal lymphopoietin (TSLP) was identified in mutant cells as a paracrine factor stimulating proliferation of neighboring non‐mutant epidermal cells, while mutant inter‐follicular epidermal (IFE) cells are lost over time. Blocking TSLP in psoriasis‐like mice reduced skin inflammation and decreased epidermal proliferation, VEGFα expression, and STAT5 activation. These findings unravel distinct roles of HF‐SCs and IFE cells in inflammatory skin disease and provide novel mechanistic insights into epidermal cell interactions in inflammation. |
| first_indexed | 2024-03-07T18:43:51Z |
| format | Article |
| id | doaj.art-c8178e4cbbe442df8147c8e7d946c4ae |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T18:43:51Z |
| publishDate | 2019-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-c8178e4cbbe442df8147c8e7d946c4ae2024-03-02T03:16:47ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842019-11-011111n/an/a10.15252/emmm.201910697Role of bulge epidermal stem cells and TSLP signaling in psoriasisNuria Gago‐Lopez0Liliana F Mellor1Diego Megías2Guillermo Martín‐Serrano3Ander Izeta4Francisco Jimenez5Erwin F Wagner6Genes, Development and Disease Group Cancer Cell Biology Programme Spanish National Cancer Research Centre (CNIO) Madrid SpainGenes, Development and Disease Group Cancer Cell Biology Programme Spanish National Cancer Research Centre (CNIO) Madrid SpainConfocal Unit at Spanish National Cancer Research Centre (CNIO) Madrid SpainBioinformatics Unit at Spanish National Cancer Research Centre (CNIO) Madrid SpainTissue Engineering Group Biodonostia Health Research Institute San Sebastian SpainGrupo de Patología Médica Mediteknia Dermatologic Clinic Universidad Fernando Pessoa Canarias Universidad Las Palmas Gran Canaria Las Palmas de Gran Canaria SpainGenes, Development and Disease Group Cancer Cell Biology Programme Spanish National Cancer Research Centre (CNIO) Madrid SpainAbstract Psoriasis is a common inflammatory skin disease involving a cross‐talk between epidermal and immune cells. The role of specific epidermal stem cell populations, including hair follicle stem cells (HF‐SCs) in psoriasis is not well defined. Here, we show reduced expression of c‐JUN and JUNB in bulge HF‐SCs in patients with scalp psoriasis. Using lineage tracing in mouse models of skin inflammation with inducible deletion of c‐Jun and JunB, we found that mutant bulge HF‐SCs initiate epidermal hyperplasia and skin inflammation. Mechanistically, thymic stromal lymphopoietin (TSLP) was identified in mutant cells as a paracrine factor stimulating proliferation of neighboring non‐mutant epidermal cells, while mutant inter‐follicular epidermal (IFE) cells are lost over time. Blocking TSLP in psoriasis‐like mice reduced skin inflammation and decreased epidermal proliferation, VEGFα expression, and STAT5 activation. These findings unravel distinct roles of HF‐SCs and IFE cells in inflammatory skin disease and provide novel mechanistic insights into epidermal cell interactions in inflammation.https://doi.org/10.15252/emmm.201910697epidermal hyper‐proliferationhair follicle stem cellslineage tracingpsoriasisthymic stromal lymphopoietin |
| spellingShingle | Nuria Gago‐Lopez Liliana F Mellor Diego Megías Guillermo Martín‐Serrano Ander Izeta Francisco Jimenez Erwin F Wagner Role of bulge epidermal stem cells and TSLP signaling in psoriasis EMBO Molecular Medicine epidermal hyper‐proliferation hair follicle stem cells lineage tracing psoriasis thymic stromal lymphopoietin |
| title | Role of bulge epidermal stem cells and TSLP signaling in psoriasis |
| title_full | Role of bulge epidermal stem cells and TSLP signaling in psoriasis |
| title_fullStr | Role of bulge epidermal stem cells and TSLP signaling in psoriasis |
| title_full_unstemmed | Role of bulge epidermal stem cells and TSLP signaling in psoriasis |
| title_short | Role of bulge epidermal stem cells and TSLP signaling in psoriasis |
| title_sort | role of bulge epidermal stem cells and tslp signaling in psoriasis |
| topic | epidermal hyper‐proliferation hair follicle stem cells lineage tracing psoriasis thymic stromal lymphopoietin |
| url | https://doi.org/10.15252/emmm.201910697 |
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