Electroacupuncture Ameliorates Knee Osteoarthritis By Rebalancing T Cell Homeostasis as Revealed By Immune Repertoire (IR) Sequencing.

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Combinatorial chemistry & high throughput screening Pub Date : 2024-08-12 DOI:10.2174/0113862073303471240805061026
Wenrui Jia, Yunan Zhang, Tianqi Wang, Cunzhi Liu, Jianfeng Tu, Guangxia Shi, LingYi Cai, Jingwen Yang, Guangrui Huang
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Abstract

Background: In this study, we used immune repertoire (IR) sequencing technology to profile the diversity of peripheral blood T cell receptors and used transcriptomics to profile the gene expression of peripheral blood neutrophil mRNA in patients with mild-moderate knee osteoarthritis (KOA) before and after electroacupuncture (EA) treatment.

Methods: An 8-week intervention with EA was performed on 3 subjects with KOA. IR sequencing of complementarity determining region 3 (CDR3) was performed using RNA extracted from peripheral blood T cells of KOA subjects prior to and at the end of the intervention, as well as healthy volunteers (controls) who matched the subjects in sex and age. Neutrophils were extracted from the plasma of healthy individuals, pretreatment patients, and posttreatment patients for further transcriptome sequencing.

Results: The D50, diversity index (DI), and Shannon entropy values of circulatory T-cells were significantly lower in pretreatment KOA patients compared to healthy controls. Posttreatment KOA samples displayed significant decreases in serum proinflammatory factors, IL-8 and IL-18 (P < 0.01), as well as a substantial reduction in serum matrix MMP-3 and MMP-13 (P < 0.01, P < 0.05). Transcriptome analysis revealed that the expression of CXCL2, IRF8, and PEAR1 (P < 0.05) was significantly higher in patients before the treatment than in the healthy population and was significantly down-regulated after the treatment. In contrast, the expression of SMPD3 (P < 0.05) showed the opposite trend.

Conclusion: EA may alleviate KOA by rebalancing T-cell homeostasis and improving systemic inflammation. At the same time, EA treatment can significantly enhance TCR diversity, reduce levels of proinflammatory factors, and increase levels of anti-inflammatory factors, thereby achieving therapeutic effects.

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电针通过重新平衡T细胞平衡改善膝骨关节炎--免疫汇聚(IR)测序揭示了这一点
研究背景在这项研究中,我们利用免疫复合物(IR)测序技术分析了外周血T细胞受体的多样性,并利用转录组学分析了轻中度膝骨关节炎(KOA)患者在电针(EA)治疗前后外周血中性粒细胞mRNA的基因表达:方法:对3名KOA患者进行为期8周的电针干预。方法:对 3 名 KOA 受试者进行了为期 8 周的 EA 干预,并使用干预前和干预结束时从 KOA 受试者以及在性别和年龄上与受试者相匹配的健康志愿者(对照组)的外周血 T 细胞中提取的 RNA 对互补决定区 3(CDR3)进行了 IR 测序。从健康人、治疗前患者和治疗后患者的血浆中提取中性粒细胞,进一步进行转录组测序:结果:与健康对照组相比,KOA治疗前患者循环T细胞的D50、多样性指数(DI)和香农熵值明显较低。治疗后的 KOA 样本显示血清促炎因子 IL-8 和 IL-18 明显降低(P < 0.01),血清基质 MMP-3 和 MMP-13 也大幅降低(P < 0.01,P < 0.05)。转录组分析显示,治疗前,患者体内的CXCL2、IRF8和PEAR1(P<0.05)的表达明显高于健康人群,治疗后则明显下调。相比之下,SMPD3(P < 0.05)的表达则呈相反趋势:结论:EA 可通过重新平衡 T 细胞平衡和改善全身炎症来缓解 KOA。结论:EA 可通过重新平衡 T 细胞稳态和改善全身炎症来缓解 KOA,同时,EA 治疗可显著提高 TCR 多样性,降低促炎因子水平,提高抗炎因子水平,从而达到治疗效果。
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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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