title: Th17 Cytokines Disrupt the Airway Mucosal Barrier in Chronic Rhinosinusitis.
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.
authors.affiliation: Department of Surgery (Otorhinolaryngology Head and Neck Surgery), The Queen Elizabeth Hospital and The University of Adelaide, Adelaide, SA 5011, Australia.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Ramezanpour
authors.affiliation: Department of Surgery (Otorhinolaryngology Head and Neck Surgery), The Queen Elizabeth Hospital and The University of Adelaide, Adelaide, SA 5011, Australia.
authors.forename: Sophia
authors.initials: S
authors.lastname: Moraitis
authors.affiliation: School of Biology, Faculty of Science and Engineering, Flinders University of South Australia, Adelaide, SA 5042, Australia.
authors.forename: Jason L P
authors.initials: JL
authors.lastname: Smith
authors.affiliation: Department of Surgery (Otorhinolaryngology Head and Neck Surgery), The Queen Elizabeth Hospital and The University of Adelaide, Adelaide, SA 5011, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Wormald
authors.affiliation: Department of Surgery (Otorhinolaryngology Head and Neck Surgery), The Queen Elizabeth Hospital and The University of Adelaide, Adelaide, SA 5011, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Vreugde
mesh_terms: D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000097:blood; D016899:Interferon-beta / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D007378:Interleukins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000378:metabolism; D012852:Sinusitis / Q000276:immunology* / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D016898:Interferon-alpha; D016899:Interferon-beta; D007371:Interferon-gamma; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22; C573415:IFNG protein, human; C406767:IL26 protein, human