Steele Lloyd, Olabi Bayanne, Roberts Kenny, Mazin Pavel V, Koplev Simon, Tudor Catherine, Rumney Benjamin, Admane Chloe, Jiang Treasa, Correa-Gallegos Donovan, Chakala Keerthi Priya, Binkevich Aljes, Gopee Nusayhah Hudaa, Predeus Alexander, Prete Martin, Winheim Elena, Annusver Karl, Forsthuber Agnes, Francis Luc, Frech Sophie, Ganier Clarisse, Layton Thomas, Liu Yingzi, Yuan Hao, Gudjonsson Johann E, Lichtenberger Beate M, Mahil Satveer, Nanchahal Jagdeep, O'Toole Edel A, Plikus Maksim V, Rinkevich Yuval, Rognoni Emanuel, Smith Catherine H, Teichmann Sarah A, Kasper Maria, Foster April R, Lotfollahi Mohammad, Haniffa Muzlifah
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Trinity College, University of Cambridge, Cambridge, UK.
Nat Immunol. 2025 Oct;26(10):1807-1820. doi: 10.1038/s41590-025-02267-8. Epub 2025 Sep 24.
Fibroblasts sculpt the architecture and cellular microenvironments of various tissues. Here we constructed a spatially resolved atlas of human skin fibroblasts from healthy skin and 23 skin diseases, with comparison to 14 cross-tissue diseases. We define six major skin fibroblast subtypes in health and three that are disease-specific. We characterize two fibroblast subtypes further as they are conserved across tissues and are immune-related. The first, F3: fibroblastic reticular cell-like fibroblast (CCL19CD74HLA-DRA), is a fibroblastic reticular cell-like subtype that is predicted to maintain the superficial perivascular immune niche. The second, F6: inflammatory myofibroblasts (IL11MMP1CXCL8IL7R), characterizes early human skin wounds, inflammatory diseases with scarring risk and cancer. F6: inflammatory myofibroblasts were predicted to recruit neutrophils, monocytes and B cells across multiple human tissues. Our study provides a harmonized nomenclature for skin fibroblasts in health and disease, contextualized with cross-tissue findings and clinical skin disease profiles.
成纤维细胞塑造了各种组织的结构和细胞微环境。在此，我们构建了一个来自健康皮肤和23种皮肤疾病的人类皮肤成纤维细胞的空间分辨图谱，并与14种跨组织疾病进行了比较。我们定义了健康状态下的六种主要皮肤成纤维细胞亚型以及三种疾病特异性亚型。我们进一步将两种成纤维细胞亚型进行了特征描述，因为它们在不同组织中保守且与免疫相关。第一种是F3：成纤维网状细胞样成纤维细胞（CCL19、CD74、HLA-DRA），是一种成纤维网状细胞样亚型，预计可维持浅表血管周围免疫微环境。第二种是F6：炎性肌成纤维细胞（IL11、MMP1、CXCL8、IL7R），其特征为早期人类皮肤伤口、有瘢痕形成风险的炎性疾病和癌症。预计F6：炎性肌成纤维细胞可在多个人类组织中募集中性粒细胞、单核细胞和B细胞。我们的研究为健康和疾病状态下的皮肤成纤维细胞提供了一个统一的命名法，并结合了跨组织研究结果和临床皮肤疾病概况。
