Interleukin-25 and mucosal T cells in noneosinophilic and eosinophilic chronic rhinosinusitis

Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease of uncertain pathogenesis. Memory T cells acquire additional functions during the secondary response and play important roles in chronic inflammation. Objective To investigate characteristics of tissue memory CD4+ T cells obtained from patients with noneosinophilic CRSwNP (NECRS) and eosinophilic CRSwNP (ECRS) by focusing on the influence of interleukin (IL)-25. Methods Pro-allergic cytokines in tissue homogenates were measured using enzyme-linked immunosorbent assays. NP mononuclear cells and CD4+ T cells were isolated from NPs from patients with CRSwNP. Cytokine expression and CD4+ T-cell subpopulations were analyzed using enzyme-linked immunosorbent assay, flow cytometry, and real-time polymerase chain reaction. Results The IL-25 level in NPs increased in patients with ECRS. IL-5 and IL-9 mRNA levels expressed by tissue CD4+ T cells were significantly elevated in patients with ECRS. Most infiltrating CD4+ T cells in ECRS and NECRS expressed CD45RO; however, regardless of the atopic status, high IL-17RB levels were detected in CD4+ T cells from patients with ECRS. IL-17RB mRNA levels expressed by tissue CD4+ T cells significantly correlated with the number of eosinophils in NPs. Elevation of IL-5 and IL-9 production was found in NP mononuclear cells from patients with ECRS, but not in those from patients with NECRS, by stimulation with IL-25 under T-cell receptor stimulation. Conclusion Interleukin-25 and a subpopulation of tissue T-helper type 2 and 9 cells that express increased IL-17RB levels could contribute to infiltration of eosinophils in NPs and could have produced the pathologic difference between NECRS and ECRS.