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

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<sup>+</sup> macrophages and CXCL13<sup>+</sup>CD4<sup>+</sup> 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<sup>+</sup> macrophages exhibit pronounced communication with CXCL13<sup>+</sup>CD4<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.

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Publication Details

Journal
Nature Communications
Published
2025-03-04
DOI
https://doi.org/10.1038/s41467-025-57361-0
Citations
28
Primary Topic
T-cell and B-cell Immunology
Type
article
Field-Weighted Citation Impact
22.33

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article

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

Chenjia He, Yun Qin, Maoxiang Qian, Qibing Xie et al.
28 citations
Nature Communications
T-cell and B-cell Immunology
22.33
article

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

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

Abstract

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<sup>+</sup> macrophages and CXCL13<sup>+</sup>CD4<sup>+</sup> 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<sup>+</sup> macrophages exhibit pronounced communication with CXCL13<sup>+</sup>CD4<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.

Nature CommunicationsVol. 16(1)
Central South University (CN), Sichuan University (CN), Fudan University (CN), Wenzhou Medical University (CN), West China Medical Center of Sichuan University (CN), Quzhou City People's Hospital (CN), West China Hospital of Sichuan University (CN), Children's Hospital of Fudan University (CN), Xiangya Hospital Central South University (CN)
National Natural Science Foundation of China, National Key Research and Development Program of China
Good health and well-being
Openalex Percentile: Top 0%
T-cell and B-cell Immunology
22.33
DOIOpen Access PDFOpenAlex
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