BACKGROUND Cystic fibrosis (CF) patients develop severe lung disease including chronic airway infections, neutrophilic inflammation, and progressive fibrotic remodeling in airways. However, cellular and molecular processes that regulate excessive collagen deposition in airways in these patients remain unclear. Fibrocytes are bone marrow (BM)-derived mesenchymal cells that express the hematopoietic cell marker CD45, and mesenchymal cell markers and implicated in collagen deposition in several fibrotic diseases. It is unknown whether fibrocytes accumulate in the lungs of CF patients, so the current study evaluates the presence of fibrocytes in the fibrotic lesions of airways in explanted CF lungs compared to non-CF unused donor lungs (control). METHODS We used immunofluorescence staining to determine if fibrocytes accumulate in explanted CF lungs compared to healthy donor lungs. Simultaneously, we evaluated cells collected by bronchoalveolar lavage (BAL) in CF patients using multi-color flow cytometry. Finally, we analyzed transcripts differentially expressed in fibrocytes isolated from the explanted CF lungs compared to control to assess fibrocyte-specific pro-fibrotic gene networks. RESULTS Our findings demonstrate fibrocyte accumulation in CF lungs compared to non-CF lungs. Additionally, fibrocytes were detected in the BAL of all CF children. Transcriptomic analysis of fibrocytes identified dysregulated genes associated with fibrotic remodeling in CF lungs. CONCLUSIONS With significantly increased fibrocytes that show increased expression of pro-fibrotic gene transcripts compared to control, our findings suggest an intervention for fibrotic remodeling as a potential therapeutic target in CF.

中文翻译：

---

囊性纤维化患者肺中的纤维细胞积聚

背景囊性纤维化（CF）患者发展为严重的肺部疾病，包括慢性气道感染、中性粒细胞炎症和气道中的进行性纤维化重塑。然而，调节这些患者气道中过度胶原沉积的细胞和分子过程仍不清楚。纤维细胞是骨髓 (BM) 衍生的间充质细胞，可表达造血细胞标记物 CD45 和间充质细胞标记物，并与几种纤维化疾病中的胶原沉积有关。目前尚不清楚纤维细胞是否在 CF 患者的肺中积聚，因此本研究评估了与非 CF 未使用的供体肺（对照）相比，移植 CF 肺气道纤维化病变中纤维细胞的存在。方法我们使用免疫荧光染色来确定与健康供体肺相比，纤维细胞是否在外植 CF 肺中积聚。同时，我们使用多色流式细胞术评估了在 CF 患者中通过支气管肺泡灌洗 (BAL) 收集的细胞。最后，我们分析了从外植 CF 肺分离的纤维细胞中与对照相比差异表达的转录物，以评估纤维细胞特异性促纤维化基因网络。结果 我们的研究结果表明，与非 CF 肺相比，CF 肺中的纤维细胞积聚。此外，在所有 CF 儿童的 BAL 中检测到纤维细胞。纤维细胞的转录组学分析确定了与 CF 肺纤维化重塑相关的失调基因。