Objective and design: IL-17 plays essential roles in neutrophilic inflammation in the lower respiratory tract, however, the characteristics of local IL-17+ T cells in nasal inflammatory mucosa are not fully understood. We investigated the roles of IL-17+ T cells in regulating neutrophil infiltration and the effect of the mucosal microenvironment in modulating IL-17+ T cell differentiation in CRSwNP tissues.
Subjects: 47 polyp tissues from chronic rhinosinusitis with nasal polyps (CRSwNP) patients without corticosteroid therapy and 26 tissues from healthy mucosa were obtained.
Methods: Immunohistochemistry and flow cytometry were used to analyze the neutrophil infiltration, local IL-17+ T cell subsets, as well as cytokine producing profiles of IL-17+ T cell; tissue homogenates were used to study neutrophil migration and IL-17+ T cell differentiation.
Results: Increase of IL-17+ cells and IL-17+ T cell subsets was significant in polyp tissues versus controls, IL-17+ cell number was positively correlated with neutrophil infiltration; while homogenates from polyp tissues with high IL-17 promoted neutrophil migration in vitro. IL-17 response was found in polyp-derived T cells upon Staphylococcus aureus infection. IL-17+ T cells were also down-regulated in polyps from patients treated with glucocorticoid steroids, and exhibited poly-functionality patterns in polyp tissues. Finally, IL-17+ T cell differentiation could be induced by IL-23, and homogenates from polyps could enhance IL-17+ T cell development.
Conclusions: This study determined a functional association of IL-17+ T cells with neutrophils in CRSwNP, and revealed that polyp microenvironment could promote IL-17+ T cell differentiation, suggesting a potential feedback role for IL-17+ T cell development and local neutrophilic inflammation.
Keywords: Chronic rhinosinusitis with nasal polyps; IL-17; IL-17+ cells; Mucosal microenvironment; Neutrophils.