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http://hdl.handle.net/10553/70070
Title: | Role of bulge epidermal stem cells and TSLP signaling in psoriasis | Authors: | Gago-Lopez, Nuria Mellor, Liliana F. Megías, Diego Martín-Serrano, Guillermo Izeta, Ander Jimenez, Francisco Wagner, Erwin F. |
UNESCO Clasification: | 320106 Dermatología | Keywords: | Epidermal Hyper-Proliferation Hair Follicle Stem Cells Lineage Tracing Psoriasis Thymic Stromal Lymphopoietin |
Issue Date: | 2019 | Journal: | EMBO Molecular Medicine | 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, VEGF alpha 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. | URI: | http://hdl.handle.net/10553/70070 | ISSN: | 1757-4676 | DOI: | 10.15252/emmm.201910697 | Source: | Embo Molecular Medicine [ISSN 1757-4676], v. 11 (11), (Noviembre 2019) |
Appears in Collections: | Artículos |
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