Genes, Development and Disease Group, Cancer Cell Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Confocal Unit at Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
EMBO Mol Med. 2019 Nov 7;11(11):e10697. doi: 10.15252/emmm.201910697. Epub 2019 Sep 26.
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.
银屑病是一种常见的炎症性皮肤疾病，涉及表皮细胞和免疫细胞之间的相互作用。特定的表皮干细胞群体，包括毛囊干细胞（HF-SCs）在银屑病中的作用尚未明确。在这里，我们发现在头皮银屑病患者的隆起 HF-SCs 中 c-JUN 和 JUNB 的表达减少。使用在皮肤炎症的小鼠模型中进行的诱导性 c-Jun 和 JunB 缺失的谱系追踪，我们发现突变的隆起 HF-SCs 引发表皮过度增生和皮肤炎症。从机制上讲，在突变细胞中鉴定出胸腺基质淋巴生成素（TSLP）作为旁分泌因子，刺激邻近非突变表皮细胞的增殖，而突变的毛囊间表皮（IFE）细胞随着时间的推移而丢失。在银屑病样小鼠中阻断 TSLP 可减少皮肤炎症，降低表皮增殖、VEGFα 表达和 STAT5 激活。这些发现揭示了 HF-SCs 和 IFE 细胞在炎症性皮肤疾病中的不同作用，并为炎症中表皮细胞相互作用提供了新的机制见解。
