Deficiency of INPP4A promotes M2 macrophage polarization in eosinophilic chronic rhinosinusitis with nasal polyps
© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:73 |
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| Enthalten in: |
Inflammation research : official journal of the European Histamine Research Society ... [et al. - 73(2024), 4 vom: 12. März, Seite 581-595 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Yingying [VerfasserIn] |
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| Links: |
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| Themen: |
E-CRSwNP |
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| Anmerkungen: |
Date Completed 29.03.2024 Date Revised 29.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00011-024-01855-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a Deficiency of INPP4A promotes M2 macrophage polarization in eosinophilic chronic rhinosinusitis with nasal polyps |
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| 520 | |a © 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a E-CRSwNP | |
| 650 | 4 | |a Eosinophil | |
| 650 | 4 | |a INPP4A | |
| 650 | 4 | |a Macrophage | |
| 650 | 4 | |a Polarization | |
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| 700 | 1 | |a Tong, Xiaoting |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Peiqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Siyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Duo |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Yulie |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Duo |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yu |e verfasserin |4 aut | |
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