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微小隐孢子虫抗原改变炎症性肠病患者分离的外周血单个核细胞中FOXP3/RORɣt表达平衡。

Syphacia obvelata antigens alter the FOXP3/RORɣt expression balance in isolated peripheral blood mononuclear cells of IBD patients.

作者信息

Amin Abbas, Taghipour Niloofar, Rostami-Nejad Mohammad, Avanaki Foroogh Alborzi, Jafarshad Reyhaneh, Tabaei Seyyed Javad Seyyed, Mosaffa Nariman

机构信息

Department of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Sci Rep. 2025 Jul 24;15(1):26871. doi: 10.1038/s41598-025-06619-0.

DOI:10.1038/s41598-025-06619-0
PMID:40701996
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12287443/
Abstract

Inflammatory Bowel Disease (IBD) arises from disrupted interactions among intestinal microbiota, epithelial cells, and the immune system, which are influenced by genetic and environmental factors. A critical factor in IBD pathogenesis is the balance between FOXP3 regulatory T cells (Tregs) and RORγt Th17 cells; a decreased Treg/Th17 ratio can lead to inflammation. Syphacia obvelata may help modulate immune responses by promoting Th2 responses and enhancing Treg populations, potentially impacting FOXP3 and RORγt expression and aiding IBD management. In this study, peripheral Blood Mononuclear Cells (PBMCs) from 6 IBD patients were treated with S. obvelata antigens (ES-Ag, S-Ag, and ES/S-Ag) for 24 h. Optimal concentrations and time points were determined via the MTT assay. Total RNA was extracted, cDNA was synthesized, and RT-qPCR was performed using FOXP3 and RORγt primers. The gene expression fold changes and FOXP3/RORγt ratios were compared to the control group. Results showed that FOXP3 expression was increased significantly after treatment with all S. obvelata antigens, including ES-Ag, S-Ag, and ES/S-Ag, whereas the expression of RORγt decreased significantly in just two groups, including ES-Ag and ES/S-Ag. Eventually, the FOXP3/RORγt gene expression fold change ratio was increased significantly after 24 h of exposure to S. obvelata antigens. Our study indicates that the ES-Ag, S-Ag, and ES/S-Ag of S. obvelata, along with their combination, can increase the FOXP3/RORɣt ratio in PBMCs from patients with IBD, suggesting anti-inflammatory effects. This finding offers hope that these antigens could be an eye-opener for developing future strategies for IBD treatment.

摘要

炎症性肠病(IBD)源于肠道微生物群、上皮细胞和免疫系统之间的相互作用紊乱,这些相互作用受遗传和环境因素影响。IBD发病机制中的一个关键因素是叉头框蛋白3(FOXP3)调节性T细胞(Tregs)和维甲酸相关孤儿受体γt(RORγt)辅助性T细胞17(Th17)之间的平衡;Treg/Th17比值降低会导致炎症。微小膜壳绦虫可能通过促进Th2反应和增加Treg群体来帮助调节免疫反应,潜在地影响FOXP3和RORγt的表达,并有助于IBD的管理。在本研究中,来自6名IBD患者的外周血单个核细胞(PBMC)用微小膜壳绦虫抗原(ES-Ag、S-Ag和ES/S-Ag)处理24小时。通过MTT法确定最佳浓度和时间点。提取总RNA,合成cDNA,并使用FOXP3和RORγt引物进行逆转录定量聚合酶链反应(RT-qPCR)。将基因表达倍数变化和FOXP3/RORγt比值与对照组进行比较。结果显示,在用所有微小膜壳绦虫抗原(包括ES-Ag、S-Ag和ES/S-Ag)处理后,FOXP3表达显著增加,而仅在两组(包括ES-Ag和ES/S-Ag)中RORγt表达显著降低。最终,在暴露于微小膜壳绦虫抗原24小时后,FOXP3/RORγt基因表达倍数变化比值显著增加。我们的研究表明,微小膜壳绦虫的ES-Ag S-Ag和ES/S-Ag及其组合可增加IBD患者PBMC中的FOXP3/RORɣt比值,表明具有抗炎作用。这一发现为这些抗原可能为未来IBD治疗策略的开发提供启示带来了希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a92f/12287443/2b527cc833cf/41598_2025_6619_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a92f/12287443/62672ad91d3e/41598_2025_6619_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a92f/12287443/2b527cc833cf/41598_2025_6619_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a92f/12287443/62672ad91d3e/41598_2025_6619_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a92f/12287443/2b527cc833cf/41598_2025_6619_Fig2_HTML.jpg

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本文引用的文献

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Epidemiology of Inflammatory Bowel Disease across the Ages in the Era of Advanced Therapies.炎症性肠病在先进治疗时代的年龄分布流行病学。
J Crohns Colitis. 2024 Oct 30;18(Supplement_2):ii3-ii15. doi: 10.1093/ecco-jcc/jjae082.
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Int J Colorectal Dis. 2024 Sep 7;39(1):139. doi: 10.1007/s00384-024-04711-x.
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Helminth-derived proteins as immune system regulators: a systematic review of their promise in alleviating colitis.
寄生虫来源的蛋白质作为免疫系统调节剂:缓解结肠炎的潜力的系统评价。
BMC Immunol. 2024 Apr 18;25(1):21. doi: 10.1186/s12865-024-00614-2.
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A PBMC-Based System to Assess Human T Cell Responses to Influenza Vaccine Candidates In Vitro.一种基于外周血单个核细胞的体外评估人类T细胞对流感疫苗候选物反应的系统。
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