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<p>Numerous patients with rheumatoid arthritis (RA) manifest severe syndromes, including elevated synovial fluid volumes (SF) with abundant immune cells, which can be controlled by TNF/JAK inhibitors. Here, we apply single-cell RNA sequencing (scRNA-seq) and subsequent validations in SF from RA patients. These analyses of synovial tissue show reduced density of SF-derived pathogenic cells (e.g., <i>SPP1</i><sup>+</sup> macrophages and <i>CXCL13</i><sup>+</sup><i>CD4</i><sup>+</sup> T cells), altered gene expression (e.g., <i>SPP1</i> and <i>STAT1</i>), molecular pathway changes (e.g., JAK/STAT), and cell-cell communications in drug-specific manners in samples from patients pre-/post-treated with adalimumab/tofacitinib. Particularly, <i>SPP1</i><sup>+</sup> macrophages exhibit pronounced communication with <i>CXCL13</i><sup>+</sup><i>CD4</i><sup>+</sup> T cells, which are abolished after treatment and correlate with treatment efficacy. These pathogenic cell types alone or in combination can augment inflammation of fibroblast-like synoviocytes in vitro, while conditional Spp1 knocking-out reduces RA-related cytokine expression in collagen-induced arthritis mice models. Our study shows the functional role of SF-derived pathogenic cells in progression and drug-specific treatment outcomes in RA.</p>

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Single cell immunoprofile of synovial fluid in rheumatoid arthritis with TNF/JAK inhibitor treatment

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月4日

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  • Xuyang Xia,
  • Chenjia He,
  • Zhinan Xue,
  • Yuelan Wang,
  • Yun Qin,
  • Zhixiang Ren,
  • Yupeng Huang,
  • Han Luo,
  • Hai-Ning Chen,
  • Wei-Han Zhang,
  • Li-Bin Huang,
  • Yunying Shi,
  • Yangjuan Bai,
  • Bei Cai,
  • Lanlan Wang,
  • Feng Zhang,
  • Maoxiang Qian,
  • Wei Zhang,
  • Yang Shu,
  • Geng Yin,
  • Heng Xu,
  • Qibing Xie

摘要

Numerous patients with rheumatoid arthritis (RA) manifest severe syndromes, including elevated synovial fluid volumes (SF) with abundant immune cells, which can be controlled by TNF/JAK inhibitors. Here, we apply single-cell RNA sequencing (scRNA-seq) and subsequent validations in SF from RA patients. These analyses of synovial tissue show reduced density of SF-derived pathogenic cells (e.g., SPP1+ macrophages and CXCL13+CD4+ T cells), altered gene expression (e.g., SPP1 and STAT1), molecular pathway changes (e.g., JAK/STAT), and cell-cell communications in drug-specific manners in samples from patients pre-/post-treated with adalimumab/tofacitinib. Particularly, SPP1+ macrophages exhibit pronounced communication with CXCL13+CD4+ T cells, which are abolished after treatment and correlate with treatment efficacy. These pathogenic cell types alone or in combination can augment inflammation of fibroblast-like synoviocytes in vitro, while conditional Spp1 knocking-out reduces RA-related cytokine expression in collagen-induced arthritis mice models. Our study shows the functional role of SF-derived pathogenic cells in progression and drug-specific treatment outcomes in RA.