Assessment of Treg/Th17 axis role in immunopathogenesis of chronic injuries of mustard lung disease

Abstract

Purpose: 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.

• Mustard lung disease
• COPD
• Th17 cells
• regulatory T cells
• immunopathogenesis

Acknowledgements

Ethical approval was obtained from the local ethical committee of Baqiyatallah Hospital, Tehran, Iran. The authors would like to express their appreciation to Baqiyatallah University of Medical Science (BMSU) for its financial support. We also wish to thank the immunohistochemistry and bronchoscopy technicians of Baqiyatallah Hospital for their assistance in the work reported here. The results described in this study were part of PhD thesis that was conducted at BMSU, Tehran, Iran.

Declaration of interest

The authors have no financial interests related to the material in the manuscript. The authors declare that there are no conflicts of interest.

The authors would like to express their appreciation to Baqiyatallah University of Medical Science (BMSU) for its financial support.