Expression profiles of regulatory and helper T-cell-associated genes in nasal polyposis
| Autor: | Z. B. Lin, Chun Wei Li, K. K. Zhang, L. Shi, De Yun Wang, Tian‐Ying Li, Yingying Li, M. A. Curotto de Lafaille |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male T cell Immunology Anti-Inflammatory Agents chemical and pharmacologic phenomena Biology Stem cell marker T-Lymphocytes Regulatory Nasal Polyps RAR-related orphan receptor gamma medicine Humans Immunology and Allergy RNA Messenger Glucocorticoids Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling CCL18 GATA3 FOXP3 hemic and immune systems T-Lymphocytes Helper-Inducer Middle Aged Eosinophil Microarray Analysis Eosinophils Interleukin 10 medicine.anatomical_structure Female |
| Zdroj: | Allergy. 67:732-740 |
| ISSN: | 0105-4538 |
| DOI: | 10.1111/j.1398-9995.2012.02811.x |
| Popis: | 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-naive 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-naive 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. |
| Databáze: | OpenAIRE |
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