Exploring the innate immune response in polycystic liver disease

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine Pub Date : 2024-11-13 DOI:10.1016/j.cyto.2024.156800
Renée Duijzer , Daisy Dalloyaux , Melissa M. Boerrigter , Heidi Lemmers , Helga Dijkstra , Liesbeth van Emst , René H.M. te Morsche , Martin Jaeger , Leo A.B. Joosten , Joost P.H. Drenth
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Abstract

Rationale

The role of the innate immune system in polycystic liver disease (PLD) has been underexplored despite its potential importance in disease progression. This study explores the innate immune response in PLD patients by analyzing cytokine production of peripheral blood mononuclear cells (PBMCs) in response to various pathogens compared to healthy controls.

Methods

Samples were collected from patients with ADPLD or ADPKD and PLD. PBMCs were isolated and stimulated with LPS (1 ng), LPS (10 ng), E. coli, K. pneumoniae, S. aureus, and C. albicans. ELISA was used to measure TNF, IL-1β, IL-1Ra, IL-6, and IL-8 concentrations after 24 hours, and IL-17, IL-22, and IFNγ concentrations after 7 days. Control samples were matched for age and gender.

Results

104 patients and 12 controls were included. PLD patients showed consistent increased IL-6 concentrations compared to controls. Other cytokine levels varied per stimulus. Controls showed higher IL-8 and TNF concentrations in response to Gram-negative bacteria, while PLD patients showed higher IL-1β and IL-1Ra levels in response to S. aureus and C. albicans. No clear differences were found in IL-17, IL-22, and IFN-γ concentrations after 7 days. These observed differences were independent of demographic and clinical parameters.

Conclusion

Compared to healthy controls, the PLD patients innate immune system shows an altered response when stimulated by various pathogens. These findings underscore the importance of further investigation into the underlying mechanisms as this might help our understanding disease progression and be a potential target for new therapies.

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探索多囊肝病的先天免疫反应。
理由:先天性免疫系统在多囊性肝病(PLD)中的作用尽管在疾病进展中具有潜在的重要性,但一直未得到充分探索。本研究通过分析外周血单核细胞(PBMCs)与健康对照组相比在应对各种病原体时产生的细胞因子,探讨多囊肝病患者的先天性免疫反应:方法:采集 ADPLD 或 ADPKD 合并 PLD 患者的样本。方法:从 ADPLD 或 ADPKD 和 PLD 患者身上采集样本,分离 PBMC,用 LPS(1 毫微克)、LPS(10 毫微克)、大肠杆菌、肺炎双球菌、金黄色葡萄球菌和白僵菌刺激 PBMC。用酶联免疫吸附法测定 24 小时后 TNF、IL-1β、IL-1Ra、IL-6 和 IL-8 的浓度,以及 7 天后 IL-17、IL-22 和 IFNγ 的浓度。对照组样本的年龄和性别均匹配:结果:共纳入 104 例患者和 12 例对照组样本。与对照组相比,PLD 患者的 IL-6 浓度持续升高。其他细胞因子水平因刺激而异。对照组对革兰氏阴性菌反应的 IL-8 和 TNF 浓度较高,而 PLD 患者对金黄色葡萄球菌和白色念球菌反应的 IL-1β 和 IL-1Ra 浓度较高。7天后,IL-17、IL-22和IFN-γ浓度没有明显差异。这些观察到的差异与人口统计学和临床参数无关:结论:与健康对照组相比,PLD 患者的先天性免疫系统在受到各种病原体刺激时表现出不同的反应。这些发现强调了进一步研究其潜在机制的重要性,因为这可能有助于我们了解疾病的进展,并成为新疗法的潜在靶点。
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来源期刊
Cytokine
Cytokine 医学-免疫学
CiteScore
7.60
自引率
2.60%
发文量
262
审稿时长
48 days
期刊介绍: The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.
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