PDF(Pubmed)
Abstract：
Interstitial lung disease (ILD) encompasses a diverse group of disorders characterized by chronic inflammation and fibrosis of the pulmonary interstitium. Three ILDs, namely idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (fHP), and connective tissue disease-associated ILD (CTD-ILD), exhibit similar progressive fibrosis phenotypes, yet possess distinct etiologies, encouraging us to explore their different underlying mechanisms.
Transcriptome data of fibrotic lung tissues from patients with IPF, fHP, and CTD-ILD were subjected to functional annotation, network, and pathway analyses. Additionally, we employed the xCell deconvolution algorithm to predict immune cell infiltration in patients with fibrotic ILDs and healthy controls.
We identified a shared progressive fibrosis-related module in these diseases which was related to extracellular matrix (ECM) degradation and production and potentially regulated by the p53 family transcription factors. In IPF, neuron-related processes emerged as a critical specific mechanism in functional enrichment. In fHP, we observed that B cell signaling and immunoglobulin A (IgA) production may act as predominant processes, which was further verified by B cell infiltration and the central role of CD19 gene. In CTD-ILD, active chemokine processes were enriched, and active dendritic cells (aDCs) were predicted to infiltrate the lung tissues.
This study revealed shared and specific molecular and cellular pathways among IPF, fHP, and CTD-ILD, providing a basis for understanding their pathogenesis and identifying potential therapeutic targets.
Transcriptome data of fibrotic lung tissues from patients with IPF, fHP, and CTD-ILD were subjected to functional annotation, network, and pathway analyses. Additionally, we employed the xCell deconvolution algorithm to predict immune cell infiltration in patients with fibrotic ILDs and healthy controls.
We identified a shared progressive fibrosis-related module in these diseases which was related to extracellular matrix (ECM) degradation and production and potentially regulated by the p53 family transcription factors. In IPF, neuron-related processes emerged as a critical specific mechanism in functional enrichment. In fHP, we observed that B cell signaling and immunoglobulin A (IgA) production may act as predominant processes, which was further verified by B cell infiltration and the central role of CD19 gene. In CTD-ILD, active chemokine processes were enriched, and active dendritic cells (aDCs) were predicted to infiltrate the lung tissues.
This study revealed shared and specific molecular and cellular pathways among IPF, fHP, and CTD-ILD, providing a basis for understanding their pathogenesis and identifying potential therapeutic targets.
摘要：
背景：间质性肺病（ILD）包括一组以慢性炎症和肺间质纤维化为特征的疾病。三个ILD，即特发性肺纤维化（IPF），纤维化过敏性肺炎（fHP），和结缔组织疾病相关ILD（CTD-ILD），表现出相似的进行性纤维化表型，但具有不同的病因，鼓励我们探索它们不同的潜在机制。
方法：IPF患者纤维化肺组织的转录组数据，fHP,和CTD-ILD进行功能注释，网络,和途径分析。此外,我们使用xCell去卷积算法预测纤维化ILD患者和健康对照者的免疫细胞浸润。
结果：我们在这些疾病中发现了一个共同的进行性纤维化相关模块，该模块与细胞外基质（ECM）降解和产生有关，并可能受到p53家族转录因子的调节。在IPF中，神经元相关过程是功能富集的关键特定机制。在fHP中，我们观察到B细胞信号转导和免疫球蛋白A（IgA）的产生可能是主要过程，B细胞浸润和CD19基因的中枢作用进一步验证。在CTD-ILD中,丰富了活性趋化因子过程，和活性树突状细胞（aDC）被预测浸润肺组织。
结论：这项研究揭示了IPF之间共有的和特定的分子和细胞途径，fHP,和CTD-ILD,为了解其发病机制和确定潜在的治疗靶点提供依据。
方法：IPF患者纤维化肺组织的转录组数据，fHP,和CTD-ILD进行功能注释，网络,和途径分析。此外,我们使用xCell去卷积算法预测纤维化ILD患者和健康对照者的免疫细胞浸润。
结果：我们在这些疾病中发现了一个共同的进行性纤维化相关模块，该模块与细胞外基质（ECM）降解和产生有关，并可能受到p53家族转录因子的调节。在IPF中，神经元相关过程是功能富集的关键特定机制。在fHP中，我们观察到B细胞信号转导和免疫球蛋白A（IgA）的产生可能是主要过程，B细胞浸润和CD19基因的中枢作用进一步验证。在CTD-ILD中,丰富了活性趋化因子过程，和活性树突状细胞（aDC）被预测浸润肺组织。
结论：这项研究揭示了IPF之间共有的和特定的分子和细胞途径，fHP,和CTD-ILD,为了解其发病机制和确定潜在的治疗靶点提供依据。
