title: Assessment of Treg/Th17 axis role in immunopathogenesis of chronic injuries of mustard lung disease.
abstract: OBJECTIVE
  Sulfur mustard (SM) lung is a heterogeneous disease associated with abnormal inflammatory immune responses. The Th17/Treg axis imbalance is associated with the pathogenesis of chronic inflammatory pulmonary disease. We aimed to determine the distribution of different Th17 and Treg cells in patients with SM lung and chronic obstructive pulmonary disease (COPD) and evaluate the clinical implications in this homeostasis.
  
  
  METHODS
  In this analytical cross-sectional study, CD4 (+) Foxp3(+ )Treg and CD4(+) IL-17(+ )Th17 cells were measured in peripheral blood mononuclear cells (PBMCs) and transbronchial biopsy (TBB) samples of 15 SM-exposed patients, 12 COPD and 13 healthy controls (HCs). The potential correlation between the ratio of Th17/Tregs and lung function was evaluated with multivariate logistic regression (MLR) analysis.
  
  
  RESULTS
  The frequency of CD4 (+) FoxP3(+) Tregs and CD4 (+) IL-17(+) Th17 was increased ∼1.7-fold (8.71/4.95) and ∼2.7-fold (1.028/0.371) respectively, in the PBMC of SM patients compared with the health controls (p < 0.001). The results indicated that there were increases in the frequency of Th17 and Tregs cells in the patients with COPD versus the HC, that is, ∼2.6-fold (0.987/0.371) and ∼1.4-fold (7.12/4.95), respectively; but they did not reach to SM level (p ≥ 0.05). Moreover, in the TBB samples, the CD4 (+) IL-17(+ )Th17 and CD4(+) FoxP3(+ )Tregs numbers were significantly higher in SM and COPD patients than HC (p < 0.05). The Th17 and Treg cells were inversely correlated with forced expiratory volume in 1s (FEV1%) (r = -0.351, p   = 0.001; r = -0.344, p = 0.021) and FEV1/FVC (r = -0.44, p = 0.001; r = -0.302, p = 0.011), respectively. Instead, positive correlations were found between Treg/Th17 ratios and forced FEV1%pred (r = 0.156, p = 0.007), as well as FEV1/FVC ratio (r = 0.334, p = 0.006).
  
  
  CONCLUSIONS
  The imbalance of Th17/Treg has a key role in immunopathogenesis of chronic phase of mustard lung disease.
authors.affiliation: a Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences , Tehran , Iran and.
authors.forename: Saber
authors.initials: S
authors.lastname: Imani
authors.affiliation: a Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences , Tehran , Iran and.
authors.forename: Jafar
authors.initials: J
authors.lastname: Salimian
authors.affiliation: b Department of Immunology , Ebn-e-Sina Research Center, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Bozorgmehr
authors.affiliation: a Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences , Tehran , Iran and.
authors.forename: Ensieh
authors.initials: E
authors.lastname: Vahedi
authors.affiliation: a Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences , Tehran , Iran and.
authors.forename: Ali
authors.initials: A
authors.lastname: Ghazvini
authors.affiliation: a Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences , Tehran , Iran and.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ghanei
authors.affiliation: a Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences , Tehran , Iran and.
authors.forename: Yunes
authors.initials: Y
authors.lastname: Panahi
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D007963:Leukocytes, Mononuclear; D008171:Lung Diseases / Q000139:chemically induced / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009151:Mustard Gas / Q000633:toxicity; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508717:IL17A protein, human; D020381:Interleukin-17; D009151:Mustard Gas
keywords: COPD; Mustard lung disease; Th17 cells; immunopathogenesis; regulatory T cells