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瑜伽维持类风湿关节炎患者 Th17/Treg 细胞平衡并降低 T 细胞衰老率:一项随机对照试验。

Yoga maintains Th17/Treg cell homeostasis and reduces the rate of T cell aging in rheumatoid arthritis: a randomized controlled trial.

机构信息

Department of Anatomy, Molecular Reproduction and Genetics Facility, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Department of Orthopaedics, Emory Musculoskeletal Institute, Emory University School of Medicine, Atlanta, USA.

出版信息

Sci Rep. 2023 Sep 11;13(1):14924. doi: 10.1038/s41598-023-42231-w.


DOI:10.1038/s41598-023-42231-w
PMID:37696876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10495372/
Abstract

The pathogenesis of rheumatoid arthritis (RA) is characterized by a Th17/Treg cell imbalance. A pro-inflammatory cytokine milieu that promotes the continued proliferation of Th17 cells is related to the development of autoinflammation. In RA, T cells have several hallmarks of cellular aging, and they accumulate DNA damage, predisposing to the occurrence of mutations and epigenetic alterations. Since the onset, progression, and treatment response are influenced by a variety of external stressors and environmental factors, this study aimed to evaluate the impact of 8-week yoga practice on disease severity, T cell subsets, markers of T cell ageing and inflammation, epigenetic alterations and gene expression patterns in active RA patients on standard disease-modifying anti-rheumatic drugs (DMARDs). A total of 64 participants with active RA were randomized into 2 groups, yoga group (n = 32) or non-yoga group (n = 32); that were assessed for disease severity, at baseline and after 8 week duration, for Disease Activity Score (DAS28-ESR), T cell subsets [Th17 (CD3+ CD4+ IL17+ RORγt+) cells and Treg (CD3+ CD4+ CD25+ CD127-Foxp3+) cells], markers of T cell aging [aged Th17 cells (CD3+ CD4+ IL17+ RORγt+ CD28-) and aged Treg cells (CD3+ CD4+ CD25+ CD127-Foxp3+ CD28-)], pro-inflammatory markers [IL-6, and IL-17], anti-inflammatory markers [TGF-β, and IL-10], epigenetic alterations [5-methyl cytosine, 5-hydroxymethyl cytosine, and HDAC1] and gene expression patterns [RORγt, FoxP3, IL-17, IL-6, TGF-β, CXCL2, CXCR2, and JUN]. In yoga group, there was a significant improvement in DAS28-ESR scores at the end of 8-weeks of yoga program. The Th17 cells and aged T cell subsets showed a significant decline whereas Treg cell population showed a significant elevation in yoga group. There were significant improvements observed in epigenetic markers as well as inflammatory markers post 8-weeks of yoga practice. The yoga group showed downregulation of RORγt, IL-17, IL-6, CXCL2, CXCR2, and upregulation of FoxP3 and TGF-β transcripts. Yoga enables the maintenance of immune-homeostasis as evident by increased Treg cell population and reduced Th17 cell population. Yoga reduces the rate of immunological aging in T cells, as seen by the reduction in population of aged Th17 cells and aged Treg cells. Yoga positively modifies transcriptome and epigenome by normalization of various inflammatory markers, gene expression patterns and epigenetic alterations. Taken together, yoga reduces RA severity, and aids in immune-modulation and hence can be beneficial as an adjunct therapy.

摘要

类风湿关节炎(RA)的发病机制以 Th17/Treg 细胞失衡为特征。促进 Th17 细胞持续增殖的促炎细胞因子环境与自身炎症的发展有关。在 RA 中,T 细胞具有细胞衰老的几个特征,并且它们积累 DNA 损伤,易发生突变和表观遗传改变。由于发病、进展和治疗反应受到多种外部应激源和环境因素的影响,本研究旨在评估 8 周瑜伽练习对活动期 RA 患者疾病严重程度、T 细胞亚群、T 细胞衰老和炎症标志物、表观遗传改变和基因表达模式的影响在标准疾病修饰抗风湿药物(DMARDs)上。共有 64 名活动期 RA 患者被随机分为瑜伽组(n=32)和非瑜伽组(n=32);在 8 周的时间内评估疾病严重程度,在基线和 8 周后评估疾病活动评分(DAS28-ESR)、T 细胞亚群[Th17(CD3+CD4+IL17+RORγt+)细胞和 Treg(CD3+CD4+CD25+CD127-Foxp3+)细胞]、T 细胞衰老标志物[衰老 Th17 细胞(CD3+CD4+IL17+RORγt+CD28-)和衰老 Treg 细胞(CD3+CD4+CD25+CD127-Foxp3+CD28-)]、促炎标志物[IL-6 和 IL-17]、抗炎标志物[TGF-β 和 IL-10]、表观遗传改变[5-甲基胞嘧啶、5-羟甲基胞嘧啶和 HDAC1]和基因表达模式[RORγt、FoxP3、IL-17、IL-6、TGF-β、CXCL2、CXCR2 和 JUN]。在瑜伽组中,在瑜伽计划 8 周结束时,DAS28-ESR 评分有显著改善。Th17 细胞和衰老的 T 细胞亚群显著下降,而 Treg 细胞群显著升高。瑜伽练习 8 周后,表观遗传标志物和炎症标志物均有显著改善。瑜伽组显示 RORγt、IL-17、IL-6、CXCL2、CXCR2 的下调和 FoxP3 和 TGF-β 转录本的上调。瑜伽通过增加 Treg 细胞群和减少 Th17 细胞群来维持免疫稳态。瑜伽减少 T 细胞的免疫衰老速度,表现为衰老 Th17 细胞和衰老 Treg 细胞的数量减少。瑜伽通过各种炎症标志物、基因表达模式和表观遗传改变的正常化来积极改变转录组和表观基因组。总之,瑜伽可降低 RA 严重程度,并有助于免疫调节,因此可作为辅助治疗的一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6caa/10495372/6b41f52d4d71/41598_2023_42231_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6caa/10495372/d1ffedcda5a9/41598_2023_42231_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6caa/10495372/1c3db82641cd/41598_2023_42231_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6caa/10495372/a3746db9bd23/41598_2023_42231_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6caa/10495372/6b41f52d4d71/41598_2023_42231_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6caa/10495372/d1ffedcda5a9/41598_2023_42231_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6caa/10495372/1c3db82641cd/41598_2023_42231_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6caa/10495372/a3746db9bd23/41598_2023_42231_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6caa/10495372/6b41f52d4d71/41598_2023_42231_Fig4_HTML.jpg

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本文引用的文献

[1]
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