Gago-Lopez, NuriaMellor Liliana, Mellor Liliana FMegias Vazquez, DiegoMartín-Serrano, GuillermoIzeta, AnderJimenez, FranciscoWagner, Erwin Friedrich2020-03-242020-03-242019-11-07EMBO Mol Med. 2019;11(11):e10697.1757-4676http://hdl.handle.net/20.500.12105/9320Psoriasis 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.engVoREpidermal hyper-proliferationHair follicle stem cellsLineage tracingPsoriasisThymic stromal lymphopoietinAtribución-NoComercial-CompartirIgual 4.0 Internacional315564821111e1069710.15252/emmm.2019106971757-4684EMBO molecular medicineopen access