Role of bulge epidermal stem cells and TSLP signaling in psoriasis

EMBO Molecular Medicine

Guillermo Martín‐Serrano¹  Diego Megías²  Liliana F Mellor³  Erwin F Wagner³  Nuria Gago‐Lopez³  Francisco Jimenez⁴  Ander Izeta⁵ 

[1] Bioinformatics Unit at Spanish National Cancer Research Centre (CNIO) Madrid Spain;Confocal Unit at Spanish National Cancer Research Centre (CNIO) Madrid Spain;Genes, Development and Disease Group Cancer Cell Biology Programme Spanish National Cancer Research Centre (CNIO) Madrid Spain;Grupo de Patología Médica Mediteknia Dermatologic Clinic Universidad Fernando Pessoa Canarias Universidad Las Palmas Gran Canaria Las Palmas de Gran Canaria Spain;Tissue Engineering Group Biodonostia Health Research Institute San Sebastian Spain;

关键词: epidermal hyper‐proliferation;    hair follicle stem cells;    lineage tracing;    psoriasis;    thymic stromal lymphopoietin;   

DOI  :  10.15252/emmm.201910697

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown