title: Differential effects of smoking and COPD upon circulating myeloid derived suppressor cells.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is characterized by an enhanced and persistent innate and acquired immune response to tobacco smoking. Myeloid-derived suppressor cells (MDSCs) modulate T-cell responses by down-modulating the T cell receptor ζ chain (TCR ζ) through the catabolism of l-arginine. The effects of smoking on MDSCs and their potential participation in COPD immunopathogenesis have not been explored so far.
  
  
  METHODS
  To investigate it, we compared the level of circulating Lineage-/HLA-DR-/CD33+/CD11b+ MDSCs, the serum concentration of arginase I (ARG I) and the expression of peripheral T-cell receptor ζ chain (TCR ζ) in never smokers, smokers with normal spirometry and COPD patients. Flow cytometry was used to quantify circulating MDSCs and TCR ζ expression. Serum ARG I levels were determined by ELISA.
  
  
  RESULTS
  The main findings of this study were that: (1) current smoking upregulates and activates circulating MDSCs both in smoker controls and COPD patients; and, (2) at variance with the smokers with normal spirometry, in patients with COPD this effect persists after quitting smoking and is accompanied by a significant and specific down-regulation of the TCR ζ chain expression in circulating T lymphocytes.
  
  
  CONCLUSIONS
  Smoking modulates circulating MDSCs. Their regulation appears altered in patients with COPD.
authors.affiliation: Fundación Investigación Sanitaria Illes Balears (FISIB), Hospital Universitari Son Espases, Palma de Mallorca, Spain; Centro de investigación biomédica en red de enfermedades respiratorias (CIBERES), Mallorca, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Scrimini
authors.forename: Jaume
authors.initials: J
authors.lastname: Pons
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí
authors.forename: Joan B
authors.initials: JB
authors.lastname: Soriano
authors.forename: Borja G
authors.initials: BG
authors.lastname: Cosio
authors.forename: Juan A
authors.initials: JA
authors.lastname: Torrecilla
authors.forename: Belén
authors.initials: B
authors.lastname: Núñez
authors.forename: Rocío
authors.initials: R
authors.lastname: Córdova
authors.forename: Amanda
authors.initials: A
authors.lastname: Iglesias
authors.forename: Andreas
authors.initials: A
authors.lastname: Jahn
authors.forename: Catalina
authors.initials: C
authors.lastname: Crespi
authors.forename: Jaume
authors.initials: J
authors.lastname: Sauleda
mesh_terms: D001119:Arginase / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D012907:Smoking / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D014797:Vital Capacity / Q000502:physiology
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; C574619:ARG1 protein, human; D001119:Arginase
keywords: ARG I; Arginase I; COPD; Chronic inflammation; Chronic obstructive pulmonary disease; MDSCs; Myeloid cells; Myeloid derived suppressor cells; PBMCs; Peripheral blood mononuclear cells; T-cell receptor ζ chain; TCR ζ