Myeloid derived suppressor cell-like fibrocytes are increased and associated with preserved lung function in COPD

Introduction: The role of fibrocytes in COPD is unknown. We sought to enumerate blood and tissue fibrocytes in COPD and determine the association of blood fibrocytes with clinical features of disease. Methods: Utilising flow cytometry to identify circulating, collagen type-1 + cells we found two populations 1) CD45 + CD34 + (fibrocytes) and 2) CD45 + CD34 - (myeloid-derived suppressor cell [MDSC]-like fibrocytes) in 41 stable COPD and 19 control subjects. Lung resection material, from a separate group of subjects, with (n=11) or without (n=11) COPD was collected for tissue fibrocyte detection. We examined circulating fibrocyte populations for correlations with clinical parameters including quantitative computed tomography (qCT) and determined pathways of association between correlated variables using a structural equation model. Results: Blood and tissue fibrocytes were not increased compared to control subjects nor were blood fibrocytes associated with lung function or qCT, but were increased in eosinophilic COPD. MDSC-like fibrocytes were increased in COPD compared to controls (3-fold [1.2-7.7], p= 0.025). Our structural equation model showed that collagen type-1 intensity for MDSC-like fibrocytes was positively associated with lung function through associations with air trapping (standardised β co-efficient -0.39, p= 0.015) predominately in the upper lobes. Conclusion: We have demonstrated that two circulating populations of fibrocyte exist in COPD, with distinct clinical associations, but are not prevalent in proximal or small airway airway tissue. Blood MDSC-like fibrocytes, however, are increased and associated with preserved lung function in COPD.