IL‐17 regulates DC migration to the peribronchial LNs and allergen presentation in experimental allergic asthma

Abstract

IL-17 is associated with different phenotypes of asthma, however, it is not fully elucidated how it influences induction and maintenance of asthma and allergy. In order to determine the role of IL-17 in development of allergic asthma, we used IL-17A/F double KO (IL-17A/F KO) and WT mice with or without neutralization of IL-17 in an experimental allergic asthma model and analyzed airway hyperresponsiveness, lung inflammation, T helper cell polarization, and DCs influx and activation. We report that the absence of IL-17 reduced influx of DCs into lungs and lung draining LNs. Compared to WT mice, IL-17A/F KO mice or WT mice after neutralization of IL-17A showed reduced airway hyperresponsiveness, eosinophilia, mucus hypersecretion, and IgE levels. DCs from draining LNs of allergen-challenged IL-17A/F KO mice showed a reduction in expression of migratory and costimulatory molecules CCR7, CCR2, MHC-II, and CD40 compared to WT DCs. Moreover, in vivo stimulation of adoptively transferred antigen-specific cells was attenuated in lung-draining LNs in the absence of IL-17. Thus, we report that IL-17 enhances airway DC activation, migration, and function. Consequently, lack of IL-17 leads to reduced antigenspecific T cell priming and impaired development of experimental allergic asthma.

Role of IL‐17 in atopy—A systematic review

“…In a double IL‐17A/F knock‐out mouse model, Jirmo et al. showed a reduced influx of dendritic cells into lungs and lung‐draining lymph nodes 38 . The authors concluded that IL‐17 enhances airway dendritic cell activation, migration, and function.…”

RNA-Seq Identifies Marked Th17 Cell Activation and Altered CFTR Expression in Different Atopic Dermatitis Subtypes in Chinese Han Populations

“…A recent study revealed that IL17A could induce nasal fibroblasts to produce thymic stromal lymphopoietin (TSLP), which promotes Th2 inflammation in AR ( 22 ). In addition, IL17A could regulate DC migration to the peribronchial lymph nodes and allergen presentation in experimental allergic asthma ( 23 ). These findings implied a close relationship between IL17A and AR in the Th2-biased cytokine microenvironment.…”

Th22 ir Th17 vaidmuo alerginių kvėpavimo takų ligų metu

“…Recent researches focused on Th17 and IL-17 contribution to type 2 low asthma, which is usually present in severe and corticosteroid-resistant asthma phenotype (33). Increased levels of IL-17 have been found in lung specimens, BALF, sputum as well as in peripheral blood of patients with severe asthma (34)(35)(36). High levels of IL-17 in asthma regulates the expression of proinflammatory cytokines and neutrophilic chemokines (34).…”

“…Increased levels of IL-17 have been found in lung specimens, BALF, sputum as well as in peripheral blood of patients with severe asthma (34)(35)(36). High levels of IL-17 in asthma regulates the expression of proinflammatory cytokines and neutrophilic chemokines (34). The regulatory mechanisms of neutrophilic inflammation are not well understood.…”

“…DCs are the key for priming and inducing T helper cell response in asthma and allergy (37). A study of the murine asthma model proposes that the presence of IL-17 in asthma and allergy leads to enhanced activation, migration, and antigen presentation by dendritic cells, which contributes to the development and the course of the disease (34). A targeted approach aimed at DC migration and activation could be aimed in IL-17 dependent asthma.…”