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Human sinonasal epithelial cells direct dendritic function and T‐cell T helper 1/T helper 2 skewing following Aspergillus exposure
Author(s) -
Mulligan Jennifer K.,
Mulligan Ryan M.,
Atkinson Carl,
Schlosser Rodney J.
Publication year - 2011
Publication title -
international forum of allergy and rhinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.503
H-Index - 46
eISSN - 2042-6984
pISSN - 2042-6976
DOI - 10.1002/alr.20055
Subject(s) - immunology , dendritic cell , cd86 , cd80 , medicine , t cell , antigen presenting cell , nasal polyps , antigen , biology , immune system , cd40 , cytotoxic t cell , in vitro , biochemistry
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. Conclusion 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. © 2011 ARS‐AAOA, LLC.