title: Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Subsets of myeloid-derived regulatory cells (MDRCs), which are phenotypically similar to the myeloid-derived suppressor cells found in patients with cancer, have recently been appreciated as critical regulators of airway inflammation in mouse models of asthma.
  
  
  OBJECTIVE
  We test the hypothesis that subsets of airway MDRCs contribute differentially to the inflammatory milieu in human asthma and chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  We used bronchoalveolar lavage to identify and characterize human airway MDRCs from 10 healthy subjects, 9 patients with mild asthma, and 8 patients with COPD, none of whom were treated with inhaled or systemic corticosteroids. We defined subsets of airway MDRCs using flow cytometry, the molecular mediators they produce, and their abilities to regulate proliferation of polyclonally activated autologous T lymphocytes.
  
  
  RESULTS
  We found substantial differences in the functional potential of MDRC subsets in healthy subjects, patients with asthma, and patients with COPD, with these differences regulated by the nitrosative and oxidative free radicals and cytokines they produced. Nitric oxide-producing MDRCs suppressed and superoxide-producing MDRCs enhanced proliferation of polyclonally activated autologous CD4 T cells. HLA-DR(+)CD11b(+)CD11c(+)CD163(-) superoxide-producing MDRCs, which stimulated proliferation of autologous T cells, comprised a high fraction of MDRCs in the airways of patients with mild asthma or COPD but not those of healthy control subjects. CD11b(+)CD14(+)CD16(-)HLA-DR(-) nitric oxide-producing MDRCs, which suppressed T-cell proliferation, were present in high numbers in airways of patients with mild asthma but not patients with COPD or healthy control subjects.
  
  
  CONCLUSIONS
  Subsets of airway MDRCs conclusively discriminate patients with mild asthma, patients with COPD, and healthy subjects from each other. The distinctive activities of these MDRCs in patients with asthma or COPD might provide novel targets for new therapeutics for these common disorders. [Corrected]
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Ala; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Ala; Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Ala; Comprehensive Arthritis, Musculoskeletal and Autoimmunity Center, University of Alabama at Birmingham, Birmingham, Ala. Electronic address: treena@uab.edu.
authors.forename: Jessy S
authors.initials: JS
authors.lastname: Deshane
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Ala; Comprehensive Arthritis, Musculoskeletal and Autoimmunity Center, University of Alabama at Birmingham, Birmingham, Ala.
authors.forename: David T
authors.initials: DT
authors.lastname: Redden
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Ala.
authors.forename: Meiqin
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Ala.
authors.forename: Marion L
authors.initials: ML
authors.lastname: Spell
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Ala; Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Ala.
authors.forename: Jaroslaw W
authors.initials: JW
authors.lastname: Zmijewski
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Ala.
authors.forename: John T
authors.initials: JT
authors.lastname: Anderson
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Ala.
authors.forename: Rohit J
authors.initials: RJ
authors.lastname: Deshane
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Ala; Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Ala.
authors.forename: Amit
authors.initials: A
authors.lastname: Gaggar
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Ala; Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Ala; Department of Surgery, University of Alabama at Birmingham, Birmingham, Ala.
authors.forename: Gene P
authors.initials: GP
authors.lastname: Siegal
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Ala; Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Ala.
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Ala.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Ala; Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Ala; Comprehensive Arthritis, Musculoskeletal and Autoimmunity Center, University of Alabama at Birmingham, Birmingham, Ala. Electronic address: dchaplin@uab.edu.
authors.forename: David D
authors.initials: DD
authors.lastname: Chaplin
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D001249:Asthma / Q000175:diagnosis* / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016022:Case-Control Studies; D002450:Cell Communication; D003937:Diagnosis, Differential; D005260:Female; D005541:Forced Expiratory Volume; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D005609:Free Radicals; D017382:Reactive Oxygen Species
keywords: Myeloid cell; macrophage; nitric oxide; regulatory T cell; superoxide