Relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma

Qing Wei,Jing Liao,Xiuan Liang,Jing Liu,Guangmin Nong,Min Jiang

doi:10.1186/s13223-020-00504-3

Abstract

BackgroundThe pathogenetic mechanisms of neutrophilic asthma are not well understood now. Whether T helper (Th)17-mediated immunity contributes to the pathogenesis of neutrophilic asthma in human is still under investigation. The aim of this study was to explore the relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma.MethodsTwenty-eight children with exacerbated asthma and without using any glucocorticoids were divided into three groups: eosinophilic asthma (EA, n = 12) group, neutrophilic asthma (NA, n = 10) group and paucigranulocytic asthma (PGA, n = 6) group according to the induced sputum cytology. Ten healthy children were recruited as healthy control (HC, n = 10) group. Peripheral Th17 and Th2 cells, and the expression of Ki-67 in peripheral Th17 cells were detected by flow cytometry. The mRNA expression of retinoic acid-related orphan receptor γt (RORγt) in peripheral blood mononuclear cells (PBMCs) was detected by qRT-PCR. The concentrations of IL-17, IL-8 and IL-5 in sputum, as well as IL-17 in plasma and culture supernatant of activated PBMCs were measured by ELISA.ResultsThe percentage of Th17 cells in peripheral Th cells, and the concentrations of IL-17, IL-8 in sputum, as well as IL-17 in culture supernatant of activated PBMCs were all increased in NA group, and positively correlated with neutrophil level in sputum and with each other. Also, the mRNA expression of RORγt in PBMCs and Ki-67 positivity in peripheral Th17 cells were both increased in NA group. The percentage of Th2 cells in peripheral Th cells, and the concentration of IL-5 in sputum were both increased in EA group, and positively correlated with eosinophil level in sputum and with each other.ConclusionsBoth Th17- and Th2-mediated immunity are involved in the pathogenesis of childhood asthma. There is predominance of Th17-mediated immunity and Th17 cells proliferation in childhood neutrophilic asthma.

Highlights

The pathogenetic mechanisms of neutrophilic asthma are not well understood
The expression of surface antigens and intracellular cytokines was measured by flow cytometry. CD4+CD8− cells were defined as T helper (Th) cells, IL-17+CD4+ CD8− T cells were defined as Th17 cells and IL-4+CD4+ CD8− T cells were defined as Th2 cells
Percentages of Th17 and Th2 cells in peripheral Th cells were significantly higher in asthmatics compared to those in healthy controls (p < 0.01), in which the percentage of Th17 cells in peripharal Th cells was significantly higher in the Neutrophilic asthma (NA) group than those in the eosinophilic asthma (EA) and paucigranulocytic asthma (PGA) groups (p < 0.01), whereas the percentage of Th2 cells in peripheral Th cells was significantly higher in the EA

Summary

Introduction

Whether T helper (Th)17-mediated immunity contributes to the pathogenesis of neutrophilic asthma in human is still under investigation. The aim of this study was to explore the relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma. It is known that T helper (Th) cells can secrete interleukins (IL-4, IL-5 and IL-13), and promote eosinophilic airway inflammation in atopic asthma [7,8,9]. It has been shown that the eosinophilic/atopic phenotype of asthma driven by Th2 mechanisms is not the only immunologic pathway contributing to asthma [7, 8]. Whether Th17-mediated immunity contributes to the pathogenesis of neutrophilic asthma in human remains to be investigated. The purpose of this study was to investigate the relationship between Th17-mediated immunity and airway inflammation in childhood with neutrophilic asthma

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Conclusion