Abstract
Cytokine mediated changes in paracellular permeability contribute to a multitude of pathological conditions including chronic rhinosinusitis (CRS). The purpose of this study was to investigate the effect of interferons and of Th1, Th2, and Th17 cytokines on respiratory epithelium barrier function. Cytokines and interferons were applied to the basolateral side of air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs) from CRS with nasal polyp patients. Transepithelial electrical resistance (TEER) and permeability of FITC-conjugated dextrans were measured over time. Additionally, the expression of the tight junction protein Zona Occludens-1 (ZO-1) was examined via immunofluorescence. Data was analysed using ANOVA, followed by Tukey HSD post hoc test. Our results showed that application of interferons and of Th1 or Th2 cytokines did not affect the mucosal barrier function. In contrast, the Th17 cytokines IL-17, IL-22, and IL-26 showed a significant disruption of the epithelial barrier, evidenced by a loss of TEER, increased paracellular permeability of FITC-dextrans, and discontinuous ZO-1 immunolocalisation. These results indicate that Th17 cytokines may contribute to the development of CRSwNP by promoting a leaky mucosal barrier.
Highlights
Chronic rhinosinusitis (CRS) is characterized by severe inflammation of the sinus mucosa leading to blockage of the nasal passageway and the accumulation of mucus and pathogens in the nose and paranasal sinuses [1, 2]
The effect of interferons and of Th1, T helper 2 (Th2), and Th17 cytokines was examined by measuring the Transepithelial electrical resistance (TEER) across human nasal epithelial cells (HNECs) monolayers from CRS patients at different time points
We compared the effect of interferons and of signature Th1, Th2, and Th17 cytokines on the barrier function of primary nasal epithelial cells harvested from CRS patients with nasal polyps
Summary
Chronic rhinosinusitis (CRS) is characterized by severe inflammation of the sinus mucosa leading to blockage of the nasal passageway and the accumulation of mucus and pathogens in the nose and paranasal sinuses [1, 2]. Cytokines regulate innate and acquired immunity [7] and can disrupt mucosal barrier function by altering tight junction (TJ) composition and structure. This occurs through signalling pathways independent of cell death and the effect is cell type specific, pleiotropic, and time and dose-dependent [8]. Th2 immune responses are characterized by the production of the interleukins IL-4, IL-5, and IL-13 [13] that are associated with the promotion of eosinophil recruitment and activation, and inhibition of several macrophage functions, providing phagocyte-independent protective responses [14]. Th17 cells act as a bridge between adaptive and innate immunity where
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