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.
Highlights
The epidermis is a stratified epithelium undergoing constant renewal due to the presence of stem cells (Alberts et al, 2002)
Previous results have reported alterations in the expression levels of c-JUN and JUNB in the inter-follicular epidermis (IFE) of psoriatic plaques from human patients (Zenz et al, 2005); it is not known whether the expression levels of c-JUN and JUNB are affected in epidermal stem cells
Reduced expression of JUNB/c-JUN in lesional regions of the inter-follicular epidermis (IFE) of psoriatic patients might be critical for the development of the disease (Zenz et al, 2005) despite the high variability in the expression of these factors (Haider et al, 2006; Park et al, 2009; Guinea-Viniegra et al, 2014)
Summary
The epidermis is a stratified epithelium undergoing constant renewal due to the presence of stem cells (Alberts et al, 2002) It is composed of the inter-follicular epidermis (IFE), which consists of layers of keratinocytes, hair follicles, and associated sebaceous and sweat glands (Fuchs, 2008). In mice, HF-SCs in the bulge region express CD34, while both HF-SCs and IFE basal keratinocytes express integrin-a6 (CD49f; Liu et al, 2003; Trempus et al, 2003; Horsley et al, 2006, 2008; Jaks et al, 2008; Jensen et al, 2009; Snippert et al, 2010) These different stem cell populations from IFE and hair follicles have distinct roles during skin remodeling, wound healing, and homeostasis. Little is known about the specific contribution of K15+ bulge HF-SCs and IFE stem cells to the development of chronic inflammatory skin diseases such as psoriasis
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