The Induction of IL-33 in the Sinus Epithelium and Its Influence on T-Helper Cell Responses.
BACKGROUND
Chronic rhinosinusitis (CRS) is characterized by epithelial activation and chronic T-cell infiltration in sinonasal mucosa and nasal polyps. IL-33 is a new cytokine of the IL-1 cytokine family that has a pro-inflammatory and Th2 type cytokine induction property. The role of IL-33 in the pathomechanisms of CRS and its interaction with other T cell subsets remain to be fully understood.


METHODS
The main trigger for IL-33 mRNA expression in primary human sinonasal epithelial cells was determined in multiple cytokine and T-cell stimulated cultures. The effects of IL-33 on naïve, Th0 and memory T-cells was studied by PCR, ELISA and flow cytometry. Biopsies from sinus tissue were analyzed by PCR and immunofluorescence for the presence of different cytokines and receptors with a special focus on IL-33.


RESULTS
IL-33 was mainly induced by IFN-γ in primary sinonasal epithelial cells, and induced a typical CRSwNP Th2 favoring cytokine profile upon co-culture with T-helper cell subsets. IL-33 and its receptor ST2 were highly expressed in the inflamed epithelial tissue of CRS patients. While IL-33 was significantly up-regulated in the epithelium for CRSsNP, its receptor was higher expressed in sinus tissue from CRSwNP.


CONCLUSIONS
The present study delineates the influence of IL-33 in upper airway epithelium and a potential role of IL-33 in chronic inflammation of CRSwNP by enhancing Th2 type cytokine production, which could both contribute to a further increase of an established Th2 profile in CRSwNP.
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; University Hospital Zurich, Department of Otorhinolaryngology, Zurich, Switzerland.
Michael B
MB
Soyka
University Hospital Zurich, Department of Otorhinolaryngology, Zurich, Switzerland.
David
D
Holzmann
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Tomasz M
TM
Basinski
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Marcin
M
Wawrzyniak
Medical University of Vienna, Department of Pediatrics, Vienna, Austria.
Christina
C
Bannert
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Simone
S
Bürgler
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Division of Pediatric Allergy and Immunology, Marmara University Medical Faculty, Istanbul, Turkey.
Tunc
T
Akkoc
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland.
Angela
A
Treis
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Beate
B
Rückert
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Mübeccel
M
Akdis
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland.
Cezmi A
CA
Akdis
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Medical University of Vienna, Department of Pediatrics, Vienna, Austria.
Thomas
T
Eiwegger
D002454:Cell Differentiation / Q000187:drug effects; D002908:Chronic Disease; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D000067596:Interleukin-33 / Q000378:metabolism*; D008954:Models, Biological; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D010256:Paranasal Sinuses / Q000473:pathology*; D012220:Rhinitis / Q000276:immunology / Q000473:pathology; D012852:Sinusitis / Q000276:immunology / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
D018836:Inflammation Mediators; D000067596:Interleukin-33; D007371:Interferon-gamma