Role of bulge epidermal stem cells and TSLP signaling in psoriasis

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation*
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Epidermal Cells / pathology*
  • Gene Knockdown Techniques
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mice
  • Psoriasis / physiopathology*
  • Signal Transduction*
  • Stem Cells / pathology*
  • Transcription Factors / metabolism

Substances

  • Cytokines
  • JunB protein, human
  • JunB protein, mouse
  • TSLP protein, human
  • Transcription Factors
  • JNK Mitogen-Activated Protein Kinases

Associated data

  • GEO/GSE119762