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抗 TNF-α 治疗后轴性脊柱关节炎患者的单细胞分析:实验数据和文献复习。

Single-Cell Analysis of Patients with Axial Spondyloarthritis After Anti-TNFα Treatment: Experimental Data and Review of the Literature.

机构信息

Medical Research Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.

School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China.

出版信息

Clin Rev Allergy Immunol. 2023 Aug;65(2):136-147. doi: 10.1007/s12016-023-08959-z. Epub 2023 Mar 8.

DOI:10.1007/s12016-023-08959-z
PMID:36884135
Abstract

Axial spondyloarthritis (Ax-SpA) is a chronic inflammatory disease that predominantly affects the axial joints and is most common in young men. However, the precise immune cell subset involved in Ax-SpA remains unclear. Our study characterized the periphery immune landscape of Ax-SpA patients before and after anti-TNFα treatment using single-cell transcriptomics and proteomics sequencing and elucidated the effects of anti-TNFα treatment at the single-cell level. First, we found that peripheral granulocytes and monocytes significantly increased in Ax-SpA patients. Second, we identified a more functional subtype of regulatory T cells, which was present in synovial fluid and increased in patients after treatment. Third, we identified a cluster of inflammatory monocyte subset with stronger inflammatory and chemotactic characteristics. A potential interaction between classical monocytes and granulocytes via the CXCL8/2-CXCR1/2 signaling pathway was observed, which decreased after treatment. Together, these results defined the complex expression profiles and advanced our understanding of the immune atlas in Ax-SpA patients before and after anti-TNFα treatment.

摘要

中轴型脊柱关节炎(Ax-SpA)是一种慢性炎症性疾病,主要影响中轴关节,在年轻男性中最为常见。然而,确切的涉及 Ax-SpA 的免疫细胞亚群仍不清楚。我们使用单细胞转录组学和蛋白质组学测序来描述抗 TNF-α 治疗前后 Ax-SpA 患者的外周免疫景观,并阐明了抗 TNF-α 治疗在单细胞水平上的作用。首先,我们发现 Ax-SpA 患者外周血粒细胞和单核细胞显著增加。其次,我们鉴定出一种更具功能的调节性 T 细胞亚型,它存在于滑液中,并在治疗后增加。第三,我们鉴定出一群具有更强炎症和趋化特征的炎性单核细胞亚群。观察到经典单核细胞和粒细胞通过 CXCL8/2-CXCR1/2 信号通路的潜在相互作用,治疗后这种相互作用减少。总之,这些结果定义了复杂的表达谱,加深了我们对抗 TNF-α 治疗前后 Ax-SpA 患者免疫图谱的理解。

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Nat Commun. 2022 Apr 1;13(1):1742. doi: 10.1038/s41467-022-29366-6.
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Nat Rev Rheumatol. 2022 Apr;18(4):205-216. doi: 10.1038/s41584-022-00761-z. Epub 2022 Mar 10.
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TGF-β-induced CD4+ FoxP3+ regulatory T cell-derived extracellular vesicles modulate Notch1 signaling through miR-449a and prevent collagen-induced arthritis in a murine model.
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