Abstract
Previous studies showed that fibrocytes are increased in the circulation and in the airway walls of chronic obstructive pulmonary disease (COPD) patients. However, it is unclear whether fibrocytes express different phenotypes. The aim of the study was to further evaluate the recruitment and phenotypic characteristics of fibrocytes in patients and murine models with COPD. By using flow cytometry analysis, blood fibrocytes were enumerated and characterized in the fresh peripheral blood samples from 10 control subjects and 25 COPD patients. Tissue fibrocytes were detected by using multiplex staining and multispectral imaging analysis in COPD patients and murine models. Our analysis revealed no significant difference in the counts of total (CD45⁺Collagen I⁺) circulating fibrocytes, or those positive for the thymic stromal lymphopoietin receptor (TSLPR) or the chemokine CXCL12 receptor (CXCR4), between COPD patients and control subjects. In contrast, a significantly higher proportion of circulating fibrocytes expressed the IL-25 receptor (IL-17RA/IL-17RB) and the IL-33 receptor (sT2L) in COPD patients compared to controls. Furthermore, we demonstrated an increase in total fibrocytes, as well as IL-17RA/IL-17RB⁺, sT2L⁺, TSLPR⁺, CXCR4⁺, and smooth muscle actin α (α-SMA)⁺ fibrocytes, within the airway walls, alveolar walls, and alveolar spaces of both COPD patients and corresponding murine models. These results indicate that fibrocytes are elevated and exhibit an activated phenotype (α-SMA-positive) in the lung tissues of patients with COPD. These cells also express receptors for IL-25, IL-33, TSLP, and CXCL12. Taken together, these findings suggest that fibrocytes may participate in the development of peribronchial and pulmonary fibrosis in COPD, potentially mediated by epithelial-derived cytokines and chemokines.