Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China.
Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China.
Cell Rep. 2024 Jul 23;43(7):114513. doi: 10.1016/j.celrep.2024.114513. Epub 2024 Jul 13.
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.
银屑病是一种难以治愈的免疫介导性疾病，会破坏皮肤屏障。虽然已有研究剖析了免疫细胞如何直接调控表皮细胞增殖的机制，但真皮成纤维细胞在银屑病进展中的作用仍不清楚。在这里，我们发现迁移到表皮-真皮交界处的树突状细胞（DCs）发出的信号通过增加细胞外基质（ECM）的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。通过单细胞 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，从而形成更硬的真皮环境。通过使用小鼠银屑病和皮肤类器官模型，我们发现了一条源自 DC 的机械化学信号通路，该通路延伸至真皮成纤维细胞，最终增强了银屑病皮肤中基底细胞的增殖。
