Th17/Treg-related cytokine imbalance in sulfur mustard exposed and stable chronic obstructive pulmonary (COPD) patients: correlation with disease activity

Abstract

In this study, we investigated expression changes of Th17/Treg-related cytokine in transbronchial lung biopsy (TBLBs) of sulfur mustard (SM) exposure, stable chronic obstructive pulmonary disease (COPD) patients and also compared it with a healthy control (HC) group. Here, ROR-γt, FoxP3, and Treg/Th17-related cytokines (IL-10, IL-17A, IL-6, and TGF-β1) were assessed using a combination of RT–QPCR and ELISA in 11 SM-exposed cases, 9 patients with GOLD stage II COPD diagnosed, and 8 HC. Our results showed that the levels of Foxp3 expression were lower and ROR-γt expression was higher in SM and COPD patients when compared with HC (all p values were less than 0.001). The relative Foxp3 expressions and Foxp3/ROR-γt ratio were positively correlated with FEV1 (%) pred (R = 0.682 and R = 0.602, respectively; p ≤ 0.001). However, the relative ROR-γt expressions were inversely correlated with FEV1 (%) pred (R= −0.75, p = 0.003) and relative Foxp3 expression (R= −0.704, p = 0.003). The mRNA and protein expression of IL-10 were significantly decreased in SM and COPD patients compared with HC (p < 0.001). An increase of IL-17A (∼7.2 fold) and TGF-β1 (∼5.6 fold) are involved in the lung exacerbation of SM and COPD patients. The expression of IL-6 was variable between three groups (p ≥ 0.05). In addition, an inverse correlation were observed between FEV1 (%) pred and expressions of IL-17A (R= −0.741), IL-6 (R= −0.673) and TGF-β1 (R= −0.632) (p ≤ 0.001). Instead, positive correlation was found between IL-10 ratios and FEV1 (%) pred (R = 0.777, p = 0.001). These findings suggest that Treg/Th17-mediated distributions are involved in the progression of chronic lung injury of SM and COPD patients.

Keywords:

• COPD
• foxp3
• immunopathogenesis
• mustard lung disease
• ROR-γt
• Treg/Th17-related cytokines

Acknowledgments

The authors thank people who provided samples. The results described in this study were part of PhD thesis that was conducted at BMSU, Tehran, Iran. We also thank the immunohistochemistry and bronchoscopy technicians of Baqiyatallah Hospital for their assistance in the work. Patient consent: Obtained.

Disclosure statement

The authors declare no conflict of interest.