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Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Deficiency of INPP4A promotes M2 macrophage polarization in eosinophilic chronic rhinosinusitis with nasal polyps
Yingying Xu1, Xiaoting Tong1, Peiqiang Liu1
1Department of Rhinology and Allergy, Otolaryngology-Head and Neck Surgery Center, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
Objective:
The treatment of eosinophilic chronic rhinosinusitis with nasal polyps (E-CRSwNP) remains a challenge due to its complex pathogenesis. Inositol polyphosphate-4-phosphatase type IA (INPP4A), a lipid phosphatase, has been implicated in allergic asthma. However, the expression and function of INPP4A in E-CRSwNP remain unclear. This study aims to investigate the role of INPP4A in macrophages in E-CRSwNP.
Methods:
We assessed the expression of INPP4A in human and mouse nasal mucosal tissues via immunofluorescence staining. THP-1 cells were cultured and exposed to various cytokines to investigate the regulation of INPP4A expression and its functional role. Additionally, we established a murine nasal polyp (NP) model and administrated an INPP4A-overexpressing lentivirus evaluate its impact on NP.
Results:
The percentage of INPP4A + CD68 + macrophages among total macrophages decreased in the E-CRSwNP group compared to the control and the non-eosinophilic CRSwNP (NE-CRSwNP) groups, exhibiting an inverse correlation with an increased percentage of CD206 + CD68 + M2 macrophages among total macrophages. Overexpression of INPP4A led to a reduced percentage of THP-1 cells polarizing towards the M2 phenotype, accompanied by decreased levels of associated chemotactic factors including CCL18, CCL22, CCL24, and CCL26. We also validated the involvement of the PI3K-AKT pathway in the function of INPP4A in vitro. Furthermore, INPP4A overexpression in the murine NP model resulted in the attenuation of eosinophilic inflammation in the nasal mucosa.
Conclusions:
INPP4A deficiency promotes macrophage polarization towards the M2 phenotype, leading to the secretion of chemokines that recruit eosinophils and Th2 cells, thereby amplifying eosinophilic inflammation in E-CRSwNP. INPP4A may exert a suppressive role in eosinophilic inflammation and could potentially serve as a novel therapeutic strategy.
Insights
Inositol polyphosphate-4-phosphatase type IA (INPP4A) deficiency promotes M2 macrophage polarization, increasing eosinophilic inflammation in chronic rhinosinusitis. INPP4A may suppress this inflammation, offering a potential therapeutic target.
Area of Science:
- Immunology
- Cell Biology
- Otorhinolaryngology
Background:
- Eosinophilic chronic rhinosinusitis with nasal polyps (E-CRSwNP) presents complex pathogenesis.
- Inositol polyphosphate-4-phosphatase type IA (INPP4A), a lipid phosphatase, is implicated in allergic asthma, but its role in E-CRSwNP is unknown.
Purpose of the Study:
- To investigate the expression and function of INPP4A in macrophages within the context of E-CRSwNP.
- To explore INPP4A's potential as a therapeutic target for E-CRSwNP.
Main Methods:
- Assessed INPP4A expression in human and mouse nasal tissues using immunofluorescence.
- Investigated INPP4A regulation and function in cytokine-stimulated THP-1 cells.
- Utilized an INPP4A-overexpressing lentivirus in a murine nasal polyp model.
Main Results:
- INPP4A+ macrophages decreased in E-CRSwNP, inversely correlating with M2 macrophages.
- INPP4A overexpression reduced M2 polarization and associated chemokine levels (CCL18, CCL22, CCL24, CCL26).
- PI3K-AKT pathway involvement was confirmed; INPP4A overexpression attenuated nasal eosinophilic inflammation in mice.
Conclusions:
- INPP4A deficiency promotes M2 macrophage polarization, amplifying eosinophilic inflammation in E-CRSwNP via chemokine secretion.
- INPP4A demonstrates a suppressive role in eosinophilic inflammation.
- INPP4A represents a potential novel therapeutic strategy for E-CRSwNP.
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