The Journal of Allergy and Clinical Immunology
Volume 121, Issue 6 , Pages 1435-1441.e3, June 2008

T-cell regulation in chronic paranasal sinus disease

  • Nicholas Van Bruaene, MD

      Affiliations

    • Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium
    • ,
  • Claudina Angela Pérez-Novo, PhD

      Affiliations

    • Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium
    • ,
  • Tomasz M. Basinski, MSc

      Affiliations

    • Swiss Institute of Allergy and Asthma Research, Davos, Switzerland
    • ,
  • Thibaut Van Zele, MD

      Affiliations

    • Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium
    • ,
  • Gabriele Holtappels

      Affiliations

    • Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium
    • ,
  • Natalie De Ruyck, MSc

      Affiliations

    • Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium
    • ,
  • Carsten Schmidt-Weber, PhD

      Affiliations

    • Swiss Institute of Allergy and Asthma Research, Davos, Switzerland
    • ,
  • Cezmi Akdis, MD

      Affiliations

    • Swiss Institute of Allergy and Asthma Research, Davos, Switzerland
    • ,
  • Paul Van Cauwenberge, MD, PhD

      Affiliations

    • Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium
    • ,
  • Claus Bachert, MD, PhD

      Affiliations

    • Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium
    • Corresponding Author InformationReprint requests: Claus Bachert, MD, PhD, Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
    • ,
  • Philippe Gevaert, MD, PhD

      Affiliations

    • Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium

Received 25 October 2007; received in revised form 14 February 2008; accepted 18 February 2008. published online 18 April 2008.

Background

Chronic rhinosinusitis is an inflammatory disease with distinct cytokine and remodeling patterns. Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a TH2-skewed eosinophilic inflammation, whereas chronic rhinosinusitis without nasal polyps (CRSsNP) represents a predominant TH1 milieu.

Objective

We aimed to study the direct tissue expression of transcription factors for T-cell subpopulations, including T regulatory cells, in relation to the cytokine expression patterns in the different disease subgroups.

Methods

The expression of forkhead box P3 (FOXP3), T-box transcription factor (T-bet), GATA-3, retinoid acid-related orphan receptor C (RORc), the suppressive cytokines TGF-β1 and IL-10, and TH1/ TH2/ TH17 cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-17) were analyzed by means of RT-PCR in 13 CRSsNP, 16 CRSwNP, and 10 control samples. Additional protein measurements were performed for TGF-β1 and IFN-γ.

Results

In CRSwNP, we observed a significantly lower FOXP3 mRNA and TGF-β1 protein expression, but a significantly higher T-bet, GATA-3, IL-5, and IL-13 mRNA expression compared with controls, whereas RORc was not significantly different compared with controls. In CRSsNP, FOXP3, T-bet, GATA-3, and RORc expression was not significantly different from controls, whereas TGF-β1 mRNA, IFN-γ mRNA, and protein were significantly higher in CRSsNP compared with controls. For IL-17, no significant differences were noted among all groups.

Conclusion

We demonstrate for the first time a decreased FOXP3 expression accompanied by an upregulation of T-bet and GATA-3 and a downregulation of TGF-β1 in CRSwNP versus controls and CRSsNP.

Key words: Chronic rhinosinusitis, FOXP3, nasal polyps, T-cell polarization, TGF-β1, transcription factors, T regulatory cell

Abbreviations used: CRSsNP, Chronic rhinosinusitis without nasal polyps, CRSwNP, Chronic rhinosinusitis with polyps, FOXP3, Forkhead box P3, IQR, Interquartile range, iTreg, Induced T regulatory, nTreg, Naturally occurring T regulatory, RORc, Retinoid acid-related orphan receptor C, T-bet, T-box transcription factor, Treg, T regulatory

 

 Supported by grants to C.B. from the Flemish Scientific Research Board, Fonds Wetenschappelijk Onderzoek, no. A12/5-HB-KH3 and G.0436.04, the Global Allergy and Asthma European Network, and the Interuniversity Attraction Poles Program–Belgian State–Belgian Science Policy, Nr. IAP P6/35, to P.G. (postdoctoral grant of the Research Foundation – Flanders [FWO]), and to Cezmi Akdis from the Swiss National Science Foundation, grant no. 32-105865.

 Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

PII: S0091-6749(08)00373-4

doi:10.1016/j.jaci.2008.02.018

The Journal of Allergy and Clinical Immunology
Volume 121, Issue 6 , Pages 1435-1441.e3, June 2008

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