The Journal of Allergy and Clinical Immunology
Volume 122, Issue 5 , Pages 961-968, November 2008

Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease

  • Nan Zhang, MD, PhD

      Affiliations

    • Upper Airway Research Laboratory (URL), Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
    • Department of Oto-Rhino-Laryngology, Zhongshan City Peoples Hospital, Zhongshan, China
    • These authors contributed equally to this work.
    • Corresponding Author InformationReprint requests: Nan Zhang, MD, PhD, Upper Airway Research Laboratory (URL), Department of Oto-Rhino-Laryngology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
  • ,
  • Thibaut Van Zele, MD, PhD

      Affiliations

    • Upper Airway Research Laboratory (URL), Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
    • These authors contributed equally to this work.
  • ,
  • Claudina Perez-Novo, PhD

      Affiliations

    • Upper Airway Research Laboratory (URL), Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
  • ,
  • Nicholas Van Bruaene, MD

      Affiliations

    • Upper Airway Research Laboratory (URL), Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
  • ,
  • Gabriele Holtappels

      Affiliations

    • Upper Airway Research Laboratory (URL), Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
  • ,
  • Natalie DeRuyck

      Affiliations

    • Upper Airway Research Laboratory (URL), Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
  • ,
  • Paul Van Cauwenberge, MD, PhD

      Affiliations

    • Upper Airway Research Laboratory (URL), Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
  • ,
  • Claus Bachert, MD, PhD

      Affiliations

    • Upper Airway Research Laboratory (URL), Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium

Received 26 February 2008; received in revised form 4 July 2008; accepted 9 July 2008. published online 22 September 2008.

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by the accumulation of inflammatory cells; however, an eosinophil predominance is seen in white (Belgian), but not Asian (south Chinese), patients with polyps.

Objective

We sought to investigate the association of inflammatory cell predominance with regulatory T-cell and T-effector cell patterns.

Methods

Nasal mucosal tissue was obtained from 26 consecutive Belgian patients with CRSwNP and 21 Belgian control subjects and 29 south Chinese patients with CRSwNP and 29 south Chinese control subjects, who all underwent phenotyping, including nasal endoscopy and computed tomographic scanning. Tissues were investigated for granulocytes and their products and T-effector/regulatory T cells and related cytokines.

Results

Both CRSwNP groups were comparable in terms of symptoms, computed tomographic scan results, and nasal endoscopy results, but asthma comorbidity was significantly higher in white patients. Tissue from white patients with CRSwNP was characterized by eosinophilic inflammation (eosinophil cationic protein/myeloperoxidase ratio > 2), whereas samples from Asian patients were biased toward neutrophilic inflammation (eosinophil cationic protein/myeloperoxidase ratio = 0.25). Both CRSwNP groups demonstrated significant upregulation of the T-cell activation marker soluble IL-2 receptor α and significant downregulation of Foxp3 expression and TGF-β1 protein content versus their respective control groups. However, whereas white patients displayed a significant increase in TH2 cytokine and related marker levels versus control subjects and versus Asian patients, the latter showed a TH1/TH17 cell pattern versus control tissue.

Conclusion

Nasal polyps (CRSwNP) from white and Asian patients are both characterized by T-cell activation and impaired regulatory T-cell function; however, T-effector cells in the samples from white patients were TH2-biased, whereas samples from their Asian counterparts demonstrated a TH1/TH17 polarization.

Key words: Airway inflammation, chronic rhinosinusitis, nasal polyps, eosinophils, TH2, TH17, regulatory T cells, IL-17A, TGF-β1, Foxp3

Abbreviations used: Be NP, Nasal polyps from Belgian patients, Be CO, Control tissue from Belgian patients, CRSwNP, Chronic rhinosinusitis with nasal polyps, CT, Computed tomography, ECP, Eosinophil cationic protein, Foxp3, Forkhead box P3, MPO, Myeloperoxidase, NP, Nasal polyp, RORC, Retinoic acid–related orphan receptor C, S-Ch CO, Control tissue from south Chinese patients, S-Ch NP, Nasal polyps from south Chinese patients, STAT, Signal transducer and activator of transcription, T-bet, T-box transcription factor

 

 Supported by grants to C.B. from the Flemish Scientific Research Board, FWO, no. A12/5-HB-KH3 and G.0436.04; the Global Allergy and Asthma European Network (GA2LEN); the Interuniversity Attraction Poles Programme–Belgian State–Belgian Science Policy, no. IAP P6/35; and a grant to N.Z. from the University of Ghent, BOF VB0149.

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

PII: S0091-6749(08)01315-8

doi:10.1016/j.jaci.2008.07.008

The Journal of Allergy and Clinical Immunology
Volume 122, Issue 5 , Pages 961-968, November 2008