d'Alessandro Miriana, Gangi Sara, Cavallaro Dalila, Bergantini Laura, Mezzasalma Fabrizio, Cattelan Stefano, Baglioni Stefano, Abbritti Marta, Cameli Paolo, Bargagli Elena
Respiratory Diseases Unit, Department of Medical and Surgical Sciences & Neurosciences, University of Siena, 53100 Siena, Italy.
Diagnostic and Interventional Bronchoscopy Unit, Cardio-Thoracic and Vascular Department, University Hospital of Siena (Azienda Ospedaliera Universitaria Senese, AOUS), 53100 Siena, Italy.
Life (Basel). 2022 May 20;12(5):762. doi: 10.3390/life12050762.
(1) Background: Sarcoidosis is a chronic multisystem disorder of unknown aetiology, driven by a T-cell mechanism allowing T-cell attachment and transmigration through the endothelium, and endorsed by the expression of an integrin alpha-E beta-7 (CD103). This study aimed to analyse the different distribution and compartmentalisation of CD103 expression on T cell subsets in BAL, peripheral blood mononuclear cells (PBMC) and lymph nodes (LLN) from sarcoidosis patients. (2) Patients: We consecutively and prospectively enrolled 14 sarcoidosis patients. We collected PBMC, LLN and BAL at the same time from all patients. Through flow cytometric analysis, we analysed the expression of CD103 on regulatory and follicular T cell subsets. (3) Results: All patients were in radiological Scadding stage II. The multivariate analysis found that the variables which most influenced the peripheral blood compartment were high CD8 and low ThReg, CD8CD103 and Tfh cell percentages. A principal component analysis plot performed to distinguish LLN, BAL and PBMC showed that they separated on the basis of CD4, CD4CD103, CD8, CD8CD103, TcEffector, TcNaive, ThNaive, ThEffector, Threg, ThregCD103, Tfh, TcfCXC5 and CD4CD103/CD4 with 65.96% of the total variance. (4) Conclusions: Our study is the first to report a link between the imbalance in circulating, alveolar and lymph node CD8 and CD8CD103 T cells, ThReg, Tfh and ThNaive and the CD103CD4/CD4 T cell ratio in the development of sarcoidosis. These findings shine a spotlight on the pathogenesis of sarcoidosis and may offer new predictors for diagnosis. Our study provides additional understanding for a personalised, and hopefully more effective treatment of sarcoidosis.
(1) 背景：结节病是一种病因不明的慢性多系统疾病，由T细胞机制驱动，允许T细胞附着并穿过内皮迁移，并由整合素α-Eβ-7（CD103）的表达所支持。本研究旨在分析结节病患者支气管肺泡灌洗（BAL）液、外周血单个核细胞（PBMC）和淋巴结（LLN）中T细胞亚群上CD103表达的不同分布和分区情况。(2) 患者：我们连续且前瞻性地纳入了14例结节病患者。我们同时从所有患者处采集了PBMC、LLN和BAL液。通过流式细胞术分析，我们分析了调节性T细胞和滤泡性T细胞亚群上CD103的表达。(3) 结果：所有患者均处于放射学Scadding II期。多变量分析发现，对外周血分区影响最大的变量是高CD8和低调节性T细胞（ThReg）、CD8⁺CD103和滤泡辅助性T细胞（Tfh）百分比。为区分LLN、BAL液和PBMC而进行的主成分分析图显示，它们基于CD4、CD4⁺CD103、CD8、CD8⁺CD103、细胞毒性效应T细胞（TcEffector）、细胞毒性初始T细胞（TcNaive）、初始辅助性T细胞（ThNaive）、效应辅助性T细胞（ThEffector）、调节性T细胞（Threg）、Threg⁺CD103、Tfh、趋化因子CXC5（TcfCXC5）以及CD4⁺CD103/CD4分离，占总方差的65.96%。(4) 结论：我们的研究首次报告了循环、肺泡和淋巴结中CD8和CD8⁺CD103 T细胞、ThReg、Tfh和ThNaive的失衡以及CD103⁺CD4/CD4 T细胞比值与结节病发生发展之间的联系。这些发现揭示了结节病的发病机制，并可能为诊断提供新的预测指标。我们的研究为结节病的个性化治疗（有望更有效）提供了更多的认识。
