Expression profiles of regulatory and helper T-cell-associated genes in nasal polyposis

• Published in: Allergy (Copenhagen) 2012-06, Vol.67 (6), p.732-740
• Main Authors: Li, C. W., Zhang, K. K., Li, T. Y., Lin, Z. B., Li, Y. Y., Curotto de Lafaille, M. A., Shi, L., Wang, D. Y.
• Format: Article
• Language: English
• Subjects: Adult; airway inflammation; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; Dermatology; Drug resistance; Eosinophils - drug effects; Eosinophils - immunology; Female; FOXP3; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; Gene Expression Profiling; Glucocorticoids - therapeutic use; Humans; Inflammatory diseases; Male; Medical sciences; Microarray Analysis; Middle Aged; nasal polyposis; Nasal Polyps - genetics; Nasal Polyps - immunology; Nasal Polyps - pathology; Nose; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Steroids; T-helper cells; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-regulatory cells; Tumors
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.2012.02811.x

Background Nasal polyposis (NP) is a Th2‐skewed inflammatory disorder, but it is unclear what role regulatory T cells (T‐reg) play in disease pathology. We investigated the expression profiles of T‐reg and T‐helper‐cell‐associated genes and their response to glucocorticosteroid (GC) treatment in Chinese patients with NP. Methods Biopsies were obtained from 29 non‐treated NP patients for comparison with inferior turbinates collected from healthy controls. In 13 patients, NP samples were collected both before and after short‐term oral GC treatment. Levels of mRNA for T‐cell markers were determined by microarray and quantitative PCR. Cellular infiltrates were assessed by histo‐ and immunohistochemistry. Results FOXP3+ T‐reg were increased in GC‐naïve NP, and numbers were negatively correlated with eosinophil infiltration. Helios staining was not detected, suggesting that FOXP3+ cells in NP are not thymus‐derived T‐reg. Compared with controls, mRNA levels corresponding to T‐reg genes were significantly increased in NP (FOXP3, TGFB1, IL10, SMAD3, IL2RA, and JAK3), but transcription factors associated with Th2 (GATA3) or Th17 responses (RORc) were significantly reduced. FOXP3 mRNA levels positively correlated with other T‐reg cell markers. Microarray analysis showed that most Th2‐related markers (e.g., Eotaxin‐1, CCL13, and CCL18) were upregulated in GC‐naïve NP vs controls. GC therapy significantly suppressed eosinophilic inflammation in NP, but did not significantly alter the expression levels of T‐reg/Th2‐associated genes. Conclusions Upregulation of FOXP3+‐inducible T‐reg cells and downregulation of Th2 and Th17 markers in NP indicate a regulatory response occurring at a site of persistent mucosal inflammation. However, immune regulation fails to control the underlying tissue pathology. Expression of T‐reg/Th2 markers after GC treatment was unaltered, suggesting that T‐cell‐driving NP inflammatory mediators are GC resistant.