Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China.
Clin Rev Allergy Immunol. 2024 Jun;66(3):274-293. doi: 10.1007/s12016-024-08997-1. Epub 2024 Jun 28.
Fibroblasts are crucial components of the skin structure. They were traditionally believed to maintain the skin's structure by producing extracellular matrix and other elements. Recent research illuminated that fibroblasts can respond to external stimuli and exhibit diverse functions, such as the secretion of pro-inflammatory factors, adipogenesis, and antigen presentation, exhibiting remarkable heterogeneity and plasticity. This revelation positions fibroblasts as active contributors to the pathogenesis of skin diseases, challenging the traditional perspective that views fibroblasts solely as structural entities. Based on their diverse functions, fibroblasts can be categorized into six subtypes: pro-inflammatory fibroblasts, myofibroblasts, adipogenic fibroblasts, angiogenic fibroblasts, mesenchymal fibroblasts, and antigen-presenting fibroblasts. Cytokines, metabolism, and epigenetics regulate functional abnormalities in fibroblasts. The dynamic changes fibroblasts exhibit in different diseases and disease states warrant a comprehensive discussion. We focus on dermal fibroblasts' aberrant manifestations and pivotal roles in inflammatory and autoimmune skin diseases, including psoriasis, vitiligo, lupus erythematosus, scleroderma, and atopic dermatitis, and propose targeting aberrantly activated fibroblasts as a potential therapeutic strategy for inflammatory and autoimmune skin diseases.
成纤维细胞是皮肤结构的重要组成部分。传统上，它们被认为通过产生细胞外基质和其他成分来维持皮肤的结构。最近的研究表明，成纤维细胞可以对外界刺激做出反应，并表现出多种功能，如促炎因子的分泌、脂肪生成和抗原呈递，表现出显著的异质性和可塑性。这一发现将成纤维细胞定位为皮肤疾病发病机制的积极参与者，挑战了将成纤维细胞仅视为结构实体的传统观点。基于其多种功能，成纤维细胞可分为六种亚型：促炎成纤维细胞、肌成纤维细胞、脂肪生成成纤维细胞、血管生成成纤维细胞、间充质成纤维细胞和抗原呈递成纤维细胞。细胞因子、代谢和表观遗传学调节成纤维细胞的功能异常。成纤维细胞在不同疾病和疾病状态下表现出的动态变化值得全面讨论。我们重点关注皮肤成纤维细胞在炎症性和自身免疫性皮肤病（如银屑病、白癜风、红斑狼疮、硬皮病和特应性皮炎）中的异常表现和关键作用，并提出靶向异常激活的成纤维细胞作为治疗炎症性和自身免疫性皮肤病的潜在策略。
