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.

中文翻译：

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隆起的表皮干细胞和TSLP信号传导在牛皮癣中的作用。

牛皮癣是一种常见的炎症性皮肤病，涉及表皮细胞与免疫细胞之间的串扰。尚未明确定义特定的表皮干细胞群体（包括毛囊干细胞（HF-SCs））在牛皮癣中的作用。在这里，我们显示头皮牛皮癣患者膨大的HF-SCs中c-JUN和JUNB的表达减少。使用世系追踪在c-Jun和JunB的诱导性缺失的皮肤炎症的小鼠模型中，我们发现突变的凸起HF-SCs启动了表皮增生和皮肤炎症。从机制上讲，胸腺基质淋巴细胞生成素（TSLP）在突变细胞中被鉴定为旁分泌因子，可刺激邻近的非突变表皮细胞增殖，而随着时间的流逝，突变的小泡间表皮细胞（IFE）丢失。在牛皮癣样小鼠中阻断TSLP可减少皮肤炎症，并降低表皮增殖，VEGFα表达和STAT5激活。这些发现揭示了HF-SCs和IFE细胞在炎症性皮肤病中的独特作用，并为炎症中的表皮细胞相互作用提供了新颖的机理见解。