Local IL-17 positive T cells are functionally associated with neutrophil infiltration and their development is regulated by mucosal microenvironment in nasal polyps

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.