T-cell regulation in chronic paranasal sinus disease

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.