Elevated Th17 cell frequencies and Th17/Treg ratio are associated with airway hyperresponsiveness in asthmatic children

Abstract

Introduction: The elevation of T helper (Th)17 cell frequencies and the imbalance of Th17/regulatory T (Treg) cells occur in asthma pathogenesis. Airway hyperresponsiveness (AHR) is a cardinal feature of asthma, and Th17 responses can promote AHR. We hypothesized that changes in Th17 cells and the Th17/Treg ratio correlate with AHR in asthmatic children.

Methods: Twenty asthmatic children and twenty healthy children were included in the study. The peak expiratory flow (PEF) % pred, forced expiratory volume in 1 s (FEV₁) % pred and the FEV₁/forced vital capacity (FVC) ratio were measured in all subjects. Methacholine challenge test (MCT) was performed in asthmatic children. Flow cytometric analysis was used to determine the proportions of Th17 and Treg cells in peripheral blood mononuclear cells. ELISA was used to assess serum levels of interleukin (IL)-17A and IL-10.

Results: Th17 cell frequencies (2.272 ± 0.207% in asthmatics, 1.193 ± 0.131% in controls, P < 0.01) and Th17/Treg ratios (0.371 ± 0.0387 in asthmatics, 0.183 ± 0.020 in controls, P < 0.01) were significantly increased in asthmatic children compared to controls. In asthmatic children, the MCT grade had positive correlations with the Th17 cell frequencies [r = 0.718, P < 0.01], serum IL-17A level [r = 0.753, P < 0.01] and Th17/Treg ratio [r = 0.721, P < 0.01], while the log₁₀PD20-FEV₁ value was negatively correlated with the Th17 cell frequencies [r = −0.654, P < 0.01], serum IL-17A level [r = −0.652, P < 0.01] and Th17/Treg ratio [r = −0.625, P < 0.01].

Conclusion: Th17 cell, IL-17A and Th17/Treg ratio were positively correlated with AHR in asthmatic children. It may be helpful to monitor Th17 cells and the Th17/Treg ratio as indicators of AHR in clinical practice.

Keywords:

• Asthma
• Th17 cells
• Treg cells
• airway hyperresponsiveness
• methacholine challenge test

Additional information

Funding

This was supported by the National Natural Science Foundation of China, Grant number: 81770030; Natural Science Foundation of Zhejiang Province, Grant number: LY15H010006; Science and Technology Department of Zhejiang Province, Grant number: 2016C33182; Medical and Health Science and Technology Project of Zhejiang Province, Grant number: 2014RCA020; Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents