title: Myeloid-derived suppressor cell-like fibrocytes are increased and associated with preserved lung function in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  The role of fibrocytes in chronic obstructive pulmonary disease (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
  Utilizing flow cytometry to identify circulating, collagen type 1+cells, we found two populations: (i) CD45+CD34+(fibrocytes) and (ii) CD45+CD34-[myeloid-derived suppressor cell (MDSC)-like fibrocytes] cells in stable COPD (n = 41) and control (n = 29) 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 path analysis 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. Myeloid-derived suppressor cell-like fibrocytes were increased in COPD compared to controls [2.3 (1.1-4.9), P = 0.038]. Our path analysis model showed that collagen type 1 intensity for MDSC-like fibrocytes was positively associated with lung function through associations with air trapping, predominately in the upper lobes.
  
  
  CONCLUSIONS
  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 tissue. Blood MDSC-like fibrocytes, however, are increased and associated with preserved lung function through a small airway-dependent mechanism in COPD.
authors.affiliation: NIHR Leicester Respiratory Biomedical Unit, Institute of Lung Health, University Hospitals of Leicester NHS Trust, Leicester, UK.|Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: A K A
authors.identifier: http://orcid.org/0000-0003-1621-1622
authors.initials: AK
authors.lastname: Wright
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: C
authors.initials: C
authors.lastname: Newby
authors.affiliation: NIHR Leicester Respiratory Biomedical Unit, Institute of Lung Health, University Hospitals of Leicester NHS Trust, Leicester, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Hartley
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: V
authors.initials: V
authors.lastname: Mistry
authors.affiliation: NIHR Leicester Respiratory Biomedical Unit, Institute of Lung Health, University Hospitals of Leicester NHS Trust, Leicester, UK.
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: R
authors.initials: R
authors.lastname: Berair
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Roach
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: R
authors.initials: R
authors.lastname: Saunders
authors.affiliation: NIHR Leicester Respiratory Biomedical Unit, Institute of Lung Health, University Hospitals of Leicester NHS Trust, Leicester, UK.
authors.forename: T
authors.initials: T
authors.lastname: Thornton
authors.affiliation: NIHR Leicester Respiratory Biomedical Unit, Institute of Lung Health, University Hospitals of Leicester NHS Trust, Leicester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Shelley
authors.affiliation: NIHR Leicester Respiratory Biomedical Unit, Institute of Lung Health, University Hospitals of Leicester NHS Trust, Leicester, UK.
authors.forename: K
authors.initials: K
authors.lastname: Edwards
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: B
authors.initials: B
authors.lastname: Barker
authors.affiliation: NIHR Leicester Respiratory Biomedical Unit, Institute of Lung Health, University Hospitals of Leicester NHS Trust, Leicester, UK.|Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: C E
authors.initials: CE
authors.lastname: Brightling
mesh_terms: D000368:Aged; D015415:Biomarkers; D016022:Case-Control Studies; D002452:Cell Count; D002454:Cell Differentiation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D000072737:Myeloid-Derived Suppressor Cells / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers
keywords: air trapping; fibrocytes; flow cytometry; ollagen type 1; path analysis model