Nasal Epithelial Cells Activated with <i>Alternaria</i> and House Dust Mite Induce Not Only Th2 but Also Th1 Immune Responses

• Main Authors: Seung-Heon Shin, Mi-Kyung Ye, Dong-Won Lee, Mi-Hyun Chae, Ba-Da Han
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: International Journal of Molecular Sciences
• Subjects: <i>Alternaria</i>; house dust mites; rhinosinusitis; nasal epithelial cell; innate lymphoid cell; transcription factor
• Online Access: https://www.mdpi.com/1422-0067/21/8/2693
• ISSN: 1661-6596; 1422-0067

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation. Airborne allergens are associated with upper and lower airway inflammatory disease. We investigated the effects of airborne allergen stimulation in the nasal epithelial cells and their effect on the peripheral blood mononuclear cells’ (PBMCs) Th immune polarization. Interleukin (IL)-10, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels were determined using the enzyme-linked immunosorbent assay (ELISA) in nasal polyp tissues. Cultured primary nasal epithelial cells were stimulated with <i>Alternaria alternata, Aspergillus fumigatus</i>, <i>Dermatophagoides pteronyssinus</i> (DP), and <i>Dermatophagoides farina</i> (DF) for 48 hours. IL-6, IL-25, IL-33, and TSLP production were measured by ELISA, and the nuclear factor-κB (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinase (MAPK) expression were determined by western blot analyses. PBMCs were cultured with nasal epithelial cell-conditioned media (NECM), and IL-5, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured. Innate lymphoid type2 cells (ILC2) were analyzed with flowcytometry. IL-25, IL-33, and TSLP levels were significantly higher in eosinophilic nasal polyps. <i>Alternaria</i>, DP, and DF enhanced IL-33 and TSLP production from the nasal epithelial cells through the NF-κB, AP-1, and MAPK pathway. NECM induced IL-5, IFN-γ, and TNF-α production from PBMCs, without increasing ILC2 expression. <i>Alternaria</i> and house dust mites enhanced the chemical mediator production from nasal epithelial cells and these allergens may induce not only Th2 inflammatory responses but also Th1 inflammatory responses in the nasal mucosa.