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T 细胞亚群的变化发生在间质性肺疾病中,并可能通过复杂的免疫级联反应对病理学产生影响。

Changes in T-cell subsets occur in interstitial lung disease and may contribute to pathology via complicated immune cascade.

机构信息

Department of Pediatric Immunology and Allergy, Medicine Faculty, Necmettin Erbakan University, Konya, Turkey.

Department of Medical Genetic, Medicine Faculty, KTO Karatay University, Konya, Turkey.

出版信息

APMIS. 2024 Sep;132(9):663-671. doi: 10.1111/apm.13445. Epub 2024 Jun 11.

Abstract

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.

摘要

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。

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