在超氧化物歧化酶a诱导炎症的实验模型中,Paricalcitol促进免疫肉芽肿的成熟。

IF 4.8 3区 医学 Q2 CELL BIOLOGY
Ablyakimov Et, Kriventsov Ma, Kubyshkin Av, Maxim A Kriventsov
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引用次数: 0

摘要

背景:肉芽肿性炎症是几种慢性炎症性疾病的标志,其特征是形成免疫性肉芽肿。维生素D受体(VDR)及其配体,如特品醇,已被证明对各种免疫细胞亚群,包括巨噬细胞、树突状细胞和t细胞具有免疫调节作用。然而,VDR激活在肉芽肿形成和相关免疫调节途径(包括PD-1/PD-L1轴)中的确切作用仍然知之甚少。本研究旨在评估选择性VDR激动剂paricalcitol对超氧化物歧化酶a (SoDA)诱导炎症实验模型中肉芽肿形成和免疫细胞组成的影响,重点关注抗原呈递细胞(包括CD68 +和CD1a +细胞)、T细胞和b细胞群以及PD-L1表达。材料与方法:- 90只雄性Wistar大鼠,分为对照组和实验组。实验动物在与SoDA致敏和完全弗氏佐剂致敏相关的不同时间点腹腔注射特维醇。对肉芽肿浸润进行组织学评估,并通过免疫组织化学使用CD68、CD3、CD1a、CD20和PD-L1等标记物评估细胞组成。统计分析包括定量形态计量学和组间比较。结果:- Paricalcitol给药显著影响肉芽肿的发展,与对照组相比,在(E1)之前或在致敏(E2)时接受治疗的组显示未成熟肉芽肿减少,成熟肉芽肿增加。观察到巨噬细胞分化增强,以多核巨细胞和上皮样细胞增加为特征。此外,治疗组肉芽肿浸润中PD-L1的表达显著增加,特别是在外周免疫细胞中。这些影响伴随着t细胞反应的调节,包括CD3 + t细胞数量的减少。结论:本研究提示,特品醇通过调节vdr介导的免疫通路促进肉芽肿稳定和成熟,包括巨噬细胞向上皮样细胞和巨大多核细胞的成熟和转化,CD1a +细胞数量的增加,以及PD-1/PD-L1轴的调节。paricalcitol通过VDR介导的途径增强PD-L1表达的能力为其在预防过度免疫反应中的作用提供了额外的证据,并强调了VDR激动剂在治疗肉芽肿性炎症中的治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Paricalcitol promotes the maturation of immune granulomas in an experimental model of superoxide dismutase A-induced inflammation.

Background: - Granulomatous inflammation is a hallmark of several chronic inflammatory diseases, characterized by the formation of immune granulomas. The vitamin D receptor (VDR) and its ligands, such as paricalcitol, have demonstrated immunomodulatory effects on various immune cell subpopulations, including macrophages, dendritic cells, and T-cells. However, the precise role of VDR activation in granuloma formation and the associated immune regulatory pathways, including the PD-1/PD-L1 axis, remains poorly understood. This study aimed to evaluate the effects of paricalcitol, a selective VDR agonist, on granuloma formation and immune cell composition in an experimental model of superoxide dismutase A (SoDA)-induced inflammation, with a focus on antigen-presenting cells (including CD68 + and CD1a + cells), T- and B-cell populations, and PD-L1 expression.

Materials and methods: - The study involved 90 male Wistar rats divided into control and experimental groups. Experimental animals received paricalcitol intraperitoneally at different time points relative to sensitization with SoDA and complete Freund's adjuvant. Granulomatous infiltrates were evaluated histologically, and the cellular composition was assessed via immunohistochemistry using markers such as CD68, CD3, CD1a, CD20, and PD-L1. Statistical analysis included quantitative morphometry and group comparisons.

Results: - Paricalcitol administration significantly influenced granuloma development, with groups receiving treatment before (E1) or at the time of sensitization (E2) showing a reduction in immature granulomas and an increase in mature granulomas compared to the control groups. Enhanced macrophage differentiation, characterized by increased multinucleated giant cells and epithelioid cells, was observed. Additionally, there was a significant increase in PD-L1 expression in granulomatous infiltrates of treated groups, particularly in peripherally located immune cells. These effects were accompanied by a modulation of T-cell responses, including a reduction in CD3 + T-cell population.

Conclusion: - The findings suggest that paricalcitol promotes granuloma stabilization and maturation by modulating VDR-mediated immune pathways, including maturation and transformation of macrophages into epithelioid and giant multinucleated cells, increase in number of CD1a + cells, and PD-1/PD-L1 axis regulation. The ability of paricalcitol to enhance PD-L1 expression through the VDR-mediated pathways provides additional evidence for its role in preventing excessive immune responses and highlights the therapeutic potential of VDR agonists in managing granulomatous inflammation.

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来源期刊
Inflammation Research
Inflammation Research 医学-免疫学
CiteScore
9.90
自引率
1.50%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
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