2024-03-28T16:49:28Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/93202023-03-24T17:42:34Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
Repisalud
author
Gago-Lopez, Nuria
author
Mellor Liliana, Mellor Liliana F
author
Megias Vazquez, Diego
author
Martín-Serrano, Guillermo
author
Izeta, Ander
author
Jimenez, Francisco
author
Wagner, Erwin Friedrich
funder
Unión Europea
funder
Instituto de Salud Carlos III
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
2020-03-24T20:00:46Z
2020-03-24T20:00:46Z
2019-11-07
EMBO Mol Med. 2019;11(11):e10697.
1757-4676
http://hdl.handle.net/20.500.12105/9320
31556482
10.15252/emmm.201910697
1757-4684
EMBO molecular medicine
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.
eng
Epidermal hyper-proliferation
Hair follicle stem cells
Lineage tracing
Psoriasis
Thymic stromal lymphopoietin
Role of bulge epidermal stem cells and TSLP signaling in psoriasis
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/9320/1/ROLEOFBULGEEPIDERMAL.201910697%281%29.pdf
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ROLEOFBULGEEPIDERMAL.201910697(1).pdf
URL
https://repisalud.isciii.es/bitstream/20.500.12105/9320/5/ROLEOFBULGEEPIDERMAL.201910697%281%29.pdf.txt
File
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text/plain
ROLEOFBULGEEPIDERMAL.201910697(1).pdf.txt