Format

Send to

Choose Destination
EMBO Mol Med. 2019 Nov 7;11(11):e10697. doi: 10.15252/emmm.201910697. Epub 2019 Sep 26.

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

Author information

1
Genes, Development and Disease Group, Cancer Cell Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
2
Confocal Unit at Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
3
Bioinformatics Unit at Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
4
Tissue Engineering Group, Biodonostia Health Research Institute, San Sebastian, Spain.
5
Grupo de Patología Médica, Mediteknia Dermatologic Clinic, Universidad Fernando Pessoa Canarias, Universidad Las Palmas Gran Canaria, Las Palmas de Gran Canaria, Spain.
6
Department of Dermatology and Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

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.

KEYWORDS:

epidermal hyper-proliferation; hair follicle stem cells; lineage tracing; psoriasis; thymic stromal lymphopoietin

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center