IL‐17A facilitates type 2 inflammation in a modified eosinophilic chronic rhinosinusitis mouse model

Abstract

AbstractBackgroundEosinophilic chronic rhinosinusitis (ECRS) is predominantly characterized by nasal type 2 inflammation. The pathogenesis of this condition is complex. High levels of IL‐17A are associated with eosinophil infiltration in some inflammatory diseases and contribute to the severity and insensitivity of corticosteroid therapy for chronic rhinosinusitis.MethodsIn the first experiment, we constructed a modified ECRS mouse model using four groups of mice: phosphate‐buffered saline (PBS)‐sensitized and nasal instillation (control); PBS‐sensitized and Staphylococcus aureus enterotoxin B (SEB) nasal instillation after nasal tamponade (SEB group); ovalbumin (OVA)‐sensitized and nasal instillation (OVA group); and OVA‐sensitized combined with OVA and SEB nasal instillation after nasal tamponade (OVA + SEB group). In the second experiment, we examined the role of IL‐17A by dividing the mice into four groups: control group; ECRS group; ECRS + anti‐IL‐17A group; and ECRS + IL‐17A group. The latter two groups received intraperitoneal injections of anti‐IL‐17A antibody or IL‐17A, respectively.ResultsWe constructed a modified ECRS mouse model (OVA + SEB group), where the IL‐17A levels were upregulated in the nasal sinus of ECRS mice and the IL‐17A levels were significantly correlated with eosinophil infiltration. We further demonstrated that IL‐17A induced type 2 inflammation and eosinophil infiltration in the ECRS group of mice. In contrast, IL‐17A neutralization attenuated type 2 inflammatory cytokine secretion and eosinophil infiltration.ConclusionOVA sensitization and unilateral nasal tamponade, combined with SEB and OVA alternate nasal instillation (OVA + SEB group), could be used to construct a more typical ECRS mouse model in which IL‐17A enhanced the expression of type 2 cytokines and eosinophil infiltration.