Department of Pediatric Immunology and Allergy, Medicine Faculty, Necmettin Erbakan University, Konya, Turkey.
Department of Medical Genetic, Medicine Faculty, KTO Karatay University, Konya, Turkey.
APMIS. 2024 Sep;132(9):663-671. doi: 10.1111/apm.13445. Epub 2024 Jun 11.
The study aimed to investigate the expression profiles of transcription factors, cytokines, and co-stimulatory molecules in helper T (Th)-cell subsets within bronchoalveolar lavage (BAL) samples of patients with interstitial lung diseases (ILDs). Twenty ILDs patients were included in the study, comprising those with idiopathic pulmonary fibrosis (IPF) (n:8), autoimmune-related ILDs (auto-ILD) (n:4), and orphan diseases (O-ILD) (n:8), alongside five control subjects. Flow cytometry was employed to evaluate the Th to cytotoxic T cell (CTL) ratio in BAL fluid, while cytopathological examination assessed macrophages, lymphocytes, and neutrophils. Quantitative real-time polymerase chain reaction was utilized to investigate the expressions in Th1, Th2, Th17, and regulatory T (Treg) cells. Results revealed elevated Th cell to CTL ratios across all patient groups compared to controls. Furthermore, upregulation of Th1, Th2, Th17, and T-cell factors was observed in all patient groups compared to controls. Interestingly, upregulation of CD28 and downregulation of CTLA-4 and PD-1 gene expression were consistent across all ILDs groups, highlighting potential immune dysregulation. This study provides a comprehensive exploration of molecular immunological mechanisms in ILDs patients, underscoring the dominance of Th2 and Th17 responses and revealing novel findings regarding the dysregulation of CD28, CTLA-4, and PD-1 expressions in ILDs for the first time.
本研究旨在探究间质性肺疾病(ILDs)患者支气管肺泡灌洗液(BAL)样本中辅助性 T(Th)细胞亚群中转录因子、细胞因子和共刺激分子的表达谱。本研究纳入了 20 名ILDs 患者,包括特发性肺纤维化(IPF)(n=8)、自身免疫相关 ILDs(auto-ILD)(n=4)和孤儿疾病(O-ILD)(n=8),以及 5 名对照受试者。采用流式细胞术评估 BAL 液中 Th 与细胞毒性 T 细胞(CTL)的比值,同时通过细胞病理学检查评估巨噬细胞、淋巴细胞和中性粒细胞。采用实时定量聚合酶链反应检测 Th1、Th2、Th17 和调节性 T(Treg)细胞中的表达。结果显示,与对照组相比,所有患者组的 Th 细胞与 CTL 比值均升高。此外,与对照组相比,所有患者组的 Th1、Th2、Th17 和 T 细胞因子表达均上调。有趣的是,所有 ILDs 组均表现出 CD28 的上调和 CTLA-4 及 PD-1 基因表达的下调,提示潜在的免疫失调。本研究全面探讨了 ILDs 患者的分子免疫学机制,强调了 Th2 和 Th17 反应的优势,并首次揭示了 CD28、CTLA-4 和 PD-1 表达在 ILDs 中失调的新发现。