Transcriptomics in synoviocytes defines pathogenesis of rheumatoid arthritis

项目摘要 风湿性关节炎（RA）是一种慢性炎症性疾病，影响全世界数百万人。疾病 进展包括滑膜的炎症，滑膜是包裹关节并含有 滑液滑膜主要由成纤维细胞组成，是RA疾病发病机制的核心。它形成 一种称为血管翳的侵入性组织，它招募免疫细胞，如T细胞和B细胞，破坏关节炎。 在关节中的软骨，并介导导致骨吸收破骨细胞活化的信号传导。在这个项目中， 我们将研究从关节置换手术中丢弃的新鲜组织中获得的滑膜成纤维细胞。我们 这项工作将通过测定单细胞基因来确定滑膜中成纤维细胞的细胞群体结构， 表达谱。在类风湿关节炎，滑膜有一个异质性的混合信号分子和细胞类型 影响免疫系统的组织和细胞之间的正反馈回路。这个项目 目的是定义一个详细的转录网络协同激活的肿瘤坏死因子（TNF）， 白细胞介素17（IL17A）。这项工作将建立有关滑膜细胞转录功能的基础知识， 因此，它可能对RA和其他由成纤维细胞介导的疾病具有广泛的意义。 结缔组织，如银屑病和间质性肺炎。

Project Summary Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects millions of people worldwide. Disease progression includes inflammation of the synovium, a membrane that encapsulates the joint and contains the synovial fluid. The synovium, composed mostly of fibroblasts, is central to disease pathogenesis in RA. It forms an invasive tissue called pannus that recruits immune cells such as T cells and B cells, destroys articular cartilage in the joint, and mediates signaling leading to activation of bone-resorbing osteoclasts. In this project, we will study synovial fibroblasts obtained from fresh tissue discarded during joint replacement surgery. Our work will define the cellular population structure of fibroblasts in the synovium by assaying single-cell gene expression profiles. In RA, the synovium has a heterogeneous mixture of signaling molecules and cell types that influence a positive feedback loop between the tissue and the cells of the immune system. This project aims to define a detailed transcriptional network synergistically activated by tumor necrosis factor (TNF) and interleukin 17 (IL17A). This work will establish basic knowledge about the transcriptional functions of synovial fibroblasts, so it may have broad implications for RA and other diseases that are mediated by fibroblasts in connective tissues such as psoriasis and interstitial pneumonia.