Indoleamine 2,3-dioxygenase ameliorates airway inflammation by
decreasing the Th17 cell response in neutrophilic asthma model
Abstract
Background: Currently, no effective treatment method is available for
neutrophilic asthma. Th17 play an important role in the promotion of
asthma inflammation. And IDO-dependent tryptophan metabolism has been
shown to act as a molecular “switch” for the conversion of Th17 cells
into Tregs under certain conditions. Objective: Therefore this study
aimed to regulate IDO expression in vivo and in vitro in a neutrophilic
asthma animal model and investigate whether IDO could reduce Th17 cells
and the secretion of related factors to ameliorate airway
hyperreactivity and inflammation in neutrophilic asthma. Methods: A
neutrophilic asthma model was established using ovalbumin(OVA)and
lipopolysaccharide. IDO expression in the model mice was regulated using
an IDO inducer and an IDO inhibitor. Th17 cells and the secretion of
related factors were examined, and changes in airway hyperreactivity and
inflammation were observed. Plasmacytoid dendritic cells and naïve CD4+
T cells were cocultured in vitro. After OVA stimulation and IDO
inhibitor treatment, changes in Th17 cells and the secretion of related
factors were examined. Results: Airway hyperreactivity and inflammation
were ameliorated in the neutrophilic asthma model mice in the IDO
induction group. IDO reduced Th17 cells and inflammatory cytokine
secretion (IL-17, IL-6, and TGF-β1). Conclusion: IDO ameliorated airway
hyperreactivity and inflammation in neutrophilic asthma. The mechanisms
may be associated with the influence of the differentiation direction of
CD4+ T (Th0) cells and inhibition of Th17 cell production. These results
will provide new bases for potential therapeutic targets for the
prevention and treatment of neutrophilic asthma using IDO.