T-cell regulation in chronic paranasal sinus disease

J Allergy Clin Immunol. 2008 Jun;121(6):1435-41, 1441.e1-3. doi: 10.1016/j.jaci.2008.02.018.

Abstract

Background: Chronic rhinosinusitis is an inflammatory disease with distinct cytokine and remodeling patterns. Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a T(H)2-skewed eosinophilic inflammation, whereas chronic rhinosinusitis without nasal polyps (CRSsNP) represents a predominant T(H)1 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-beta1 and IL-10, and T(H)1/ T(H)2/ T(H)17 cytokines (IFN-gamma, 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-beta1 and IFN-gamma.

Results: In CRSwNP, we observed a significantly lower FOXP3 mRNA and TGF-beta1 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-beta1 mRNA, IFN-gamma 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-beta1 in CRSwNP versus controls and CRSsNP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chronic Disease
  • Cytokines / biosynthesis
  • Enzyme-Linked Immunosorbent Assay
  • Forkhead Transcription Factors / biosynthesis
  • GATA3 Transcription Factor / biosynthesis
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Nasal Polyps / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhinitis / immunology*
  • Sinusitis / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology*
  • Transcription Factors / biosynthesis

Substances

  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • GATA3 Transcription Factor
  • Transcription Factors