牛皮癣是一种顽固性免疫介导疾病，会破坏皮肤屏障。虽然研究已经剖析了免疫细胞直接调节表皮细胞增殖的机制，但真皮成纤维细胞在牛皮癣进展中的参与仍不清楚。在这里，我们发现来自迁移到真皮-表皮交界区的树突状细胞（DC）的信号通过增加细胞外基质（ECM）表达来增强真皮硬度，从而进一步促进基底表皮细胞过度增殖。我们分析了细胞间相互作用，观察到 DC 和成纤维细胞之间的相互作用比 DC 和表皮细胞之间的相互作用更强。使用单细胞 RNA (scRNA) 测序、空间转录组学、免疫染色和硬度测量，我们发现 DC 分泌的 LGALS9 可以被 CD44+ 真皮成纤维细胞接收，导致 ECM 表达增加，从而创造更坚硬的真皮环境。通过采用小鼠银屑病和皮肤类器官模型，我们发现了一条源自树突状细胞、延伸至真皮成纤维细胞并最终增强银屑病皮肤基底细胞增殖的机械化学信号传导途径。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Psoriasis is an intractable immune-mediated disorder that disrupts the skin barrier. While studies have dissected the mechanism by which immune cells directly regulate epidermal cell proliferation, the involvement of dermal fibroblasts in the progression of psoriasis remains unclear. Here, we identified that signals from dendritic cells (DCs) that migrate to the dermal-epidermal junction region enhance dermal stiffness by increasing extracellular matrix (ECM) expression, which further promotes basal epidermal cell hyperproliferation. We analyzed cell-cell interactions and observed stronger interactions between DCs and fibroblasts than between DCs and epidermal cells. Using single-cell RNA (scRNA) sequencing, spatial transcriptomics, immunostaining, and stiffness measurement, we found that DC-secreted LGALS9 can be received by CD44+ dermal fibroblasts, leading to increased ECM expression that creates a stiffer dermal environment. By employing mouse psoriasis and skin organoid models, we discovered a mechano-chemical signaling pathway that originates from DCs, extends to dermal fibroblasts, and ultimately enhances basal cell proliferation in psoriatic skin.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.