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Role of bulge epidermal stem cells and TSLP signaling in psoriasis.

EMBO molecular medicine | 2019

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.

Pubmed ID: 31556482 RIS Download

Associated grants

  • Agency: Marie Curie Actions of the European Union´s Seventh Framework Programme (FP7/2007-2013), International
    Id: 608765
  • Agency: Spanish Ministry of Economy and Competitiveness, International
    Id: SAF2015-70857RE
  • Agency: Institute of Health Carlos III, International
    Id: PI16/01430
  • Agency: EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC), International
    Id: ERC-AdG 2016 CSI-Fun
  • Agency: European Regional Development Fund, International

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