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Published on: June 8, 2012
Responses of Nasal Polyp-Derived Macrophages to Inflammatory Cues and Potential Pathological Roles in Type 2 Chronic
Hyunkyung Cha1, Ara Jo2, Hee-Suk Lim2
1Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
Objectives:
The role of highly plastic and heterogeneous macrophages in the pathogenesis of nasal polyps (NP) is not well understood. We aimed to investigate the distribution and responses of NP-derived macrophages to inflammatory cues according to endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP).
Methods:
The distribution of macrophage subsets was analyzed using NP bulk RNA sequencing data with CIBERSORTx program. The cytokines and chemokines produced by NP-derived macrophages following stimulation with interleukin (IL)-4, staphylococcal enterotoxin B (SEB), and lipopolysaccharide were evaluated using a multiplex cytokine assay. Immunofluorescence staining in NP tissues was conducted to validate the findings.
Results:
Type 2 CRSwNP exhibited a significantly higher proportion of M2 macrophages, whereas both M1 and M2 macrophage populations were elevated in non-type 2 CRSwNP. Baseline cytokine analysis of NP-derived macrophages revealed an increase in thymic stromal lymphopoietin (TSLP) levels in CRSwNP compared to controls. Furthermore, TSLP expression was significantly upregulated from baseline levels following IL-4 or SEB stimulation in type 2 CRSwNP. Notably, IL-4 stimulation led to an increase in oncostatin M (OSM) only in type 2 CRSwNP. Additionally, the number and proportion of TSLP- and OSM-expressing cells among CD163-positive cells were significantly higher in the NP of type 2 CRSwNP patients.
Conclusion:
NP-derived macrophages from type 2 CRSwNP exhibit elevated expression of TSLP and OSM in response to IL-4 or SEB, potentially contributing to the pathophysiology of type 2 CRSwNP.
Insights
Macrophages in nasal polyps (NP) play a key role in chronic rhinosinusitis with nasal polyps (CRSwNP). Type 2 CRSwNP shows elevated TSLP and OSM from macrophages, suggesting a role in disease.
Area of Science:
- Immunology
- Pathophysiology
- Molecular Biology
Background:
- Macrophages are crucial in nasal polyp (NP) pathogenesis, but their heterogeneity and role in different chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes remain unclear.
- Understanding macrophage behavior is vital for targeted therapies in CRSwNP.
Purpose of the Study:
- To investigate the distribution and inflammatory responses of macrophages derived from nasal polyps (NP) in relation to CRSwNP endotypes.
- To elucidate the specific roles of macrophage subsets and their cytokine production in Type 2 (T2) CRSwNP.
Main Methods:
- Analysis of macrophage subset distribution in NP using bulk RNA sequencing and CIBERSORTx.
- Evaluation of cytokine and chemokine production by NP-derived macrophages upon stimulation with IL-4, SEB, and LPS.
- Immunofluorescence staining of NP tissues to validate findings.
Main Results:
- Type 2 (T2) CRSwNP demonstrated a higher proportion of M2 macrophages compared to non-type 2 (NT2) CRSwNP.
- NP-derived macrophages showed increased baseline TSLP levels in CRSwNP patients.
- TSLP and OSM expression were significantly upregulated in T2 CRSwNP macrophages upon IL-4 or SEB stimulation, with higher TSLP/OSM-expressing cells in T2 NP tissues.
Conclusions:
- Macrophages in T2 CRSwNP exhibit distinct responses, with elevated TSLP and OSM expression.
- These findings suggest that NP-derived macrophages, particularly in T2 CRSwNP, contribute to the disease's pathophysiology through specific cytokine profiles.
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