title: Human sinonasal epithelial cells direct dendritic function and T-cell T helper 1/T helper 2 skewing following Aspergillus exposure.
abstract: BACKGROUND
  In lower airway disease such as asthma, epithelial cells have been shown to be potent regulators of dendritic cell (DC) functions. However, it is unclear how human sinonasal epithelial cells (HSNECs) from patients with sinusitis regulate DC functions. Therefore, in these studies we investigated the ability of Aspergillus fumigatus exposed HSNECs to regulate DC antigen uptake, maturation, and direction of T-cell T helper 1 (Th1)/Th2 skewing.
  
  
  METHODS
  Primary HSNECs were cultured from control (n = 8), chronic sinusitis without nasal polyps (CRSsNP) (n = 9), and chronic sinusitis with nasal polyps (CRSwNP) (n = 7) patients and exposed to Aspergillus. Conditioned media was placed upon monocyte-derived DCs from healthy controls. DC antigen uptake was assessed by dextran-fluorescein isothiocyanate (FITC) uptake. DC differentiation and maturation was assessed by immunostaining for CD209, CD80, and CD86 followed by flow cytometric analysis. DC direction of T-cell Th1/Th2 skewing was evaluated by immunostaining followed by intracellular flow cytometric analysis for interferon (IFN)-γ and interleukin (IL)-5.
  
  
  RESULTS
  Control and CRSsNP HSNECs have the capacity to stimulate DC antigen uptake, differentiation, and maturation following Aspergillus exposure. CRSwNP HSNECs stimulate DC activation independent of Aspergillus exposure. Furthermore, Aspergillus-exposed CRSwNP HSNECs skew T-cells toward a Th2 phenotype.
  
  
  CONCLUSIONS
  CRSwNP-derived HSNECs stimulate DC maturation and Th2 skewing independent of Aspergillus exposure. However, control and CRSsNP HSNECs induce DC maturation and Th2 skewing after Aspergillus exposure. These in vitro studies demonstrate that HSNECs are key regulators of DC functions in the sinus microenvironment.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA. konopa@musc.edu
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Mulligan
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Mulligan
authors.forename: Carl
authors.initials: C
authors.lastname: Atkinson
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Schlosser
mesh_terms: D000946:Antigens, Fungal / Q000276:immunology; D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002908:Chronic Disease; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology; D009298:Nasal Polyps / Q000276:immunology; D010641:Phenotype; D012852:Sinusitis / Q000276:immunology*; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*
chemical_list: D000946:Antigens, Fungal; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015848:Interleukin-5; D007371:Interferon-gamma