T-cell regulation in chronic paranasal sinus disease

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• 作者：Nicholas Van Bruaene ; Claudina Angela Pé ; rez-Novo ; Tomasz M. Basinski ; Thibaut Van Zele ; Gabriele Holtappels ; Natalie De Ruyck ; Carsten Schmidt-Weber ; Cezmi Akdis ; Paul Van Cauwenberge ; Claus Bachert ; Philippe Gevaert
• 关键词：Chronic rhinosinusitis ; FOXP3 ; nasal polyps ; T-cell polarization ; TGF-β ; 1 ; transcription factors ; T regulatory cell
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2008
• 出版时间：June 2008
• 年：2008
• 卷：121
• 期：6
• 页码：1435-1441.e3
• 全文大小：760 K

文摘

Background

Chronic rhinosinusitis is an inflammatory disease with distinct cytokine and remodeling patterns. Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a T_H2-skewed eosinophilic inflammation, whereas chronic rhinosinusitis without nasal polyps (CRSsNP) represents a predominant T_H1 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 T_H1/ T_H2/ T_H17 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.