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Th2 cytokines associated with chronic rhinosinusitis with polyps down-regulate the antimicrobial immune function of
Murugappan Ramanathan1, Won-Kyung Lee, Ernst W Spannhake
1Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21287-0910, USA.
Background:
Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a disorder characterized by persistent eosinophilic Th2 inflammation and frequent sinonasal microbial colonization. It has been postulated that an abnormal mucosal immune response underlies disease pathogenesis. The relationship between Th2 inflammatory cytokines and the innate immune function of sinonasal epithelial cells (SNECs) has not been explored.
Methods:
Human SNECs (HSNECs) isolated from control subjects and patients with CRS were assessed for expression of antimicrobial innate immune genes and proinflammatory cytokine genes by real-time polymerase chain reaction, ELISA, and flow cytometry. A model of the Th2 inflammatory environment was created by exposure of primary HSNEC to the Th2 cytokine interleukin (IL)-4 or IL-13 for 36 hours, with subsequent assessment of innate immune gene expression.
Results:
HSNEC obtained from CRSwNP patients displayed decreased expression of multiple antimicrobial innate immune markers, including toll-like receptor 9, human beta-defensin 2, and surfactant protein A. Baseline expression of these genes by normal and CRS HSNEC in culture is significantly down-regulated after incubation with IL-4 or IL-13.
Conclusion:
Expression of multiple innate immune genes by HSNEC is reduced in CRSwNP. One mechanism appears to be a direct effect of the leukocyte-derived Th2 cytokines present in the sinonasal mucosa in CRSwNP. Impaired mucosal innate immunity may contribute to microbial colonization and abnormal immune responses associated with CRSwNP.
Insights
Chronic rhinosinusitis with nasal polyps (CRSwNPs) involves reduced innate immune genes in sinonasal epithelial cells. Th2 cytokines like IL-4 and IL-13 directly impair these immune responses, potentially leading to colonization and abnormal immunity.
Area of Science:
- Immunology
- Otolaryngology
- Microbiology
Background:
- Chronic rhinosinusitis with nasal polyps (CRSwNPs) is linked to Th2 inflammation and microbial colonization.
- The role of Th2 cytokines in sinonasal epithelial cell (SNEC) innate immunity is unclear.
- Abnormal mucosal immune responses are suspected in CRSwNP pathogenesis.
Purpose of the Study:
- To investigate the expression of innate immune genes in human SNECs (HSNECs) from CRSwNP patients.
- To determine the effect of Th2 cytokines (IL-4, IL-13) on HSNEC innate immune function.
Main Methods:
- HSNECs from controls and CRSwNP patients were analyzed for innate immune and inflammatory gene expression.
- Real-time PCR, ELISA, and flow cytometry were used for gene expression analysis.
- HSNECs were cultured and exposed to IL-4 or IL-13 to model Th2 inflammation.
Main Results:
- CRSwNP HSNECs showed reduced expression of antimicrobial innate immune markers (TLR9, HBD2, SP-A).
- Exposure to IL-4 or IL-13 significantly downregulated baseline innate immune gene expression in HSNECs.
- Th2 cytokines directly impact innate immune gene expression in sinonasal epithelium.
Conclusions:
- Reduced expression of innate immune genes in HSNECs is characteristic of CRSwNP.
- Leukocyte-derived Th2 cytokines in the sinonasal mucosa contribute to impaired innate immunity.
- Impaired mucosal innate immunity may facilitate microbial colonization and aberrant immune responses in CRSwNP.
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