Unravelling T-cell dynamics and immune responses in initial and recurrent uveitis.

IF 4.1 4区 医学 Q2 IMMUNOLOGY
Scandinavian Journal of Immunology Pub Date : 2024-12-01 Epub Date: 2024-11-07 DOI:10.1111/sji.13417
Zhiruo Wang, Yuanyuan Yang, Guochun Chen, Gong Chen, Jing Luo, Yunping Li, Jingming Shi, Huihui Chen
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Abstract

This study aimed to identify novel serological targets and investigate immune responses in patients with non-infectious uveitis, focusing on differences between initial onset and recurrent episodes. Differential gene expression analysis, immunocyte typing and T-cell receptor (TCR) gene analysis were conducted on RNA-sequenced peripheral blood samples from healthy individuals (n = 6) and non-infectious uveitis patients (n = 12), divided into 6 patients each at initial onset and recurrent stages. Peripheral blood T-cell types were analysed using flow cytometry. Bioinformatics methods included tools for RNA sequencing data processing, CIBERSORT for immune cell type prediction and specialized software for TCR repertoire analysis. Findings indicated that individuals with recurrent uveitis demonstrated a stronger adaptive immune response and a more pronounced immune imbalance compared to those with initial onset. Memory T cells were predominant in recurrent episodes, suggesting their potential role as biomarkers for disease progression. Significant differences in TCR diversity and V(D)J gene usage were observed between the various uveitis groups and healthy controls. Importantly, 38 uveitis-specific TCR sequences showed substantial expansion in the uveitis patients compared to controls. An elevated expansion of these specific TCR sequences was associated with an increased risk of uveitis development. The study highlights the critical role of adaptive immune responses and specific immune cell types in the pathogenesis of recurrent uveitis. Identification of the uveitis-specific TCR repertoire set could provide deeper insights into the disease and facilitate the development of targeted therapies for uveitis patients.

揭示初次和复发性葡萄膜炎的 T 细胞动态和免疫反应。
本研究旨在确定新的血清学靶点,并调查非感染性葡萄膜炎患者的免疫反应,重点关注初次发病与复发之间的差异。研究人员对健康人(6 人)和非感染性葡萄膜炎患者(12 人)的 RNA 序列外周血样本进行了差异基因表达分析、免疫细胞分型和 T 细胞受体(TCR)基因分析,将初发期和复发期患者各分为 6 人。使用流式细胞术分析外周血 T 细胞类型。生物信息学方法包括 RNA 测序数据处理工具、用于免疫细胞类型预测的 CIBERSORT 和用于 TCR 重排分析的专用软件。研究结果表明,与初次发病者相比,复发性葡萄膜炎患者表现出更强的适应性免疫反应和更明显的免疫失衡。记忆T细胞在复发性葡萄膜炎患者中占主导地位,这表明它们有可能成为疾病进展的生物标志物。不同葡萄膜炎组别与健康对照组在TCR多样性和V(D)J基因使用方面存在显著差异。重要的是,与对照组相比,38 个葡萄膜炎特异性 TCR 序列在葡萄膜炎患者中出现了大幅扩增。这些特异性 TCR 序列的扩增与葡萄膜炎发病风险的增加有关。这项研究强调了适应性免疫反应和特异性免疫细胞类型在复发性葡萄膜炎发病机制中的关键作用。对葡萄膜炎特异性 TCR 重排集的鉴定可加深人们对该疾病的了解,并促进针对葡萄膜炎患者的靶向疗法的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.70
自引率
5.40%
发文量
109
审稿时长
1 months
期刊介绍: This peer-reviewed international journal publishes original articles and reviews on all aspects of basic, translational and clinical immunology. The journal aims to provide high quality service to authors, and high quality articles for readers. The journal accepts for publication material from investigators all over the world, which makes a significant contribution to basic, translational and clinical immunology.
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