Th17 cytokines: novel potential therapeutic targets for COPD pathogenesis and exacerbations

Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways caused mainly by cigarette smoke exposure. COPD progression is marked by exacerbations of the disease, often associated with infections. Recent data show the involvement in COPD pathophysiology of interleukin (IL)-17 and IL-22, two cytokines that are important in the control of lung inflammation and infection. During the initiation and progression of the disease, increased IL-17 secretion causes neutrophil recruitment, leading to chronic inflammation, airways obstruction and emphysema. In the established phase of COPD, a defective IL-22 response facilitates pathogen-associated infections and disease exacerbations. Altered production of these cytokines involves a complex network of immune cells and dysfunction of antigen-presenting cells. In this review, we describe current knowledge on the involvement of IL-17 and IL-22 in COPD pathophysiology at steady state and during exacerbations, and discuss implications for COPD management and future therapeutic approaches.

Genetic variants in IL17A and serum levels of IL-17A are associated with COPD related to tobacco smoking and biomass burning

“…Additionally, in the same study with a knockout murine model, they suppressed Il17a and observed that neutrophilia was attenuated in comparison with wild-type mice, suggesting an important role of this cytokine in neutrophilic inflammation 46 . This finding suggests that IL-17A could be (in the future) a novel therapeutic target to attenuate neutrophilia present in airways in acute exacerbations 47 . However, more investigations are required.…”

IL-17–high asthma with features of a psoriasis immunophenotype

“…In support of this concept, evidence points to the IL-17 pathway being upregulated in patients with chronic obstructive pulmonary disease, a disease characterized by neutrophilic inflammation and caused primarily by smoking. 36 A recent study of asthmatic smokers, combining an in vivo analysis of IL-17A expression and exposure of epithelial cells ex vivo to cigarette smoke extract, has supported that smoking induces neutrophilia through IL-17 induction. 37 Furthermore, smoking is known to contribute to alterations of microbiota and epithelial barrier function.…”

Updates on T helper type 17 immunity in respiratory disease

“…Mice overexpressing IL‐17 have more severe emphysema to cigarette smoke exposure, and Il17ra −/− mice are protected against cigarette‐smoke‐induced emphysema . Both IL‐17A and the number of IL‐17 + CD4 + T cells have studies in COPD and this has been recently summarized in a review by Le Rouzic et al . The antigen specificity of these cells remains to be determined because some of these cells could be specific to the abnormal microbiome in the COPD lung or against host‐derived proteins such as elastin fragments, in which some investigators have considered COPD as an autoimmune disease.…”

“…found that IL‐17 mediated virus‐induced neutrophilic inflammation as well as exacerbating airspace enlargement, suggesting that IL‐17 pathway may also be involved in viral‐mediated COPD exacerbations. Data supporting an interventional trial and the risk and benefits of targeting IL‐17 have been recently reviewed . A review of clinicaltrials.gov lists several observational trials to study T‐cell responses and IL‐17 and IL‐22 as biomarkers in COPD (NCT00281229 and NCT02655302).…”