Wang Liangzhe, Wang Bo, Kou Erwen, Du Lin, Zhu Yuanjie
Department of Dermatology, Naval Medical Center, Naval Medical University, Shanghai, China.
Front Immunol. 2023 Sep 22;14:1259515. doi: 10.3389/fimmu.2023.1259515. eCollection 2023.
The skin is exposed to environmental challenges and contains heterogeneous cell populations such as epithelial cells, stromal cells, and skin-resident immune cells. As the most abundant type of stromal cells, fibroblasts have been historically considered silent observers in the immune responses of the cutaneous epithelial immune microenvironment (EIME), with little research conducted on their heterogeneity and immune-related functions. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have overcome the limitations of bulk RNA sequencing and help recognize the functional and spatial heterogeneity of fibroblasts, as well as their crosstalk with other types of cells in the cutaneous EIME. Recently, emerging single-cell sequencing data have demonstrated that fibroblasts notably participate in the immune responses of the EIME and impact the initiation and progression of inflammatory skin diseases. Here, we summarize the latest advances in the role of fibroblasts in the cutaneous EIME of inflammatory skin diseases and discuss the distinct functions and molecular mechanisms of activated fibroblasts in fibrotic skin diseases and non-fibrotic inflammatory skin diseases. This review help unveil the multiple roles of fibroblasts in the cutaneous EIME and offer new promising therapeutic strategies for the management of inflammatory skin diseases by targeting fibroblasts or the fibroblast-centered EIME.
皮肤暴露于环境挑战之下，包含多种异质性细胞群体，如上皮细胞、基质细胞和皮肤驻留免疫细胞。作为最丰富的基质细胞类型，成纤维细胞在历史上一直被视为皮肤上皮免疫微环境（EIME）免疫反应中的沉默旁观者，对其异质性和免疫相关功能的研究很少。单细胞RNA测序（scRNA-seq）和空间转录组学（ST）克服了批量RNA测序的局限性，有助于识别成纤维细胞的功能和空间异质性，以及它们与皮肤EIME中其他类型细胞的相互作用。最近，新出现的单细胞测序数据表明，成纤维细胞显著参与EIME的免疫反应，并影响炎症性皮肤病的发生和发展。在这里，我们总结了成纤维细胞在炎症性皮肤病皮肤EIME中的作用的最新进展，并讨论了活化成纤维细胞在纤维化皮肤病和非纤维化炎症性皮肤病中的不同功能和分子机制。这篇综述有助于揭示成纤维细胞在皮肤EIME中的多种作用，并通过靶向成纤维细胞或以成纤维细胞为中心的EIME，为炎症性皮肤病的治疗提供新的有前景的治疗策略。
