IL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte
Abstract Background Previous studies have shown that IL-25 levels are increased in patients with asthma with fixed airflow limitation (FAL). However, the mechanism by which IL-25 contributes to airway remodeling and FAL remains unclear. Here, we hypothesized that IL-25 facilitates pro-fibrotic pheno...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-023-02509-z |
| _version_ | 1827708831866552320 |
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| author | Xiujuan Yao Qinglin Chen Xiangdong Wang Xiaofang Liu Luo Zhang |
| author_facet | Xiujuan Yao Qinglin Chen Xiangdong Wang Xiaofang Liu Luo Zhang |
| author_sort | Xiujuan Yao |
| collection | DOAJ |
| description | Abstract Background Previous studies have shown that IL-25 levels are increased in patients with asthma with fixed airflow limitation (FAL). However, the mechanism by which IL-25 contributes to airway remodeling and FAL remains unclear. Here, we hypothesized that IL-25 facilitates pro-fibrotic phenotypic changes in bronchial epithelial cells (BECs) and circulating fibrocytes (CFs), orchestrates pathological crosstalk from BECs to CFs, and thereby contributes to airway remodeling and FAL. Methods Fibrocytes from asthmatic patients with FAL and chronic asthma murine models were detected using flow cytometry, multiplex staining and multispectral imaging analysis. The effect of IL-25 on BECs and CFs and on the crosstalk between BECs and CFs was determined using cell culture and co-culture systems. Results We found that asthmatic patients with FAL had higher numbers of IL-25 receptor (i.e., IL-17RB)+-CFs, which were negatively correlated with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). The number of airway IL-17RB+-fibrocytes was significantly increased in ovalbumin (OVA)- and IL-25-induced asthmatic mice versus the control subjects. BECs stimulated with IL-25 exhibited an epithelial-mesenchymal transition (EMT)-like phenotypic changes. CFs stimulated with IL-25 produced high levels of extracellular matrix (ECM) proteins and connective tissue growth factors (CTGF). These profibrotic effects of IL-25 were partially blocked by the PI3K-AKT inhibitor LY294002. In the cell co-culture system, OVA-challenged BECs facilitated the migration and expression of ECM proteins and CTGF in CFs, which were markedly blocked using an anti-IL-17RB antibody. Conclusion These results suggest that IL-25 may serve as a potential therapeutic target for asthmatic patients with FAL. |
| first_indexed | 2024-03-10T17:10:21Z |
| format | Article |
| id | doaj.art-a14818a0b75d48acbebec1eee34ec1ea |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-10T17:10:21Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-a14818a0b75d48acbebec1eee34ec1ea2023-11-20T10:40:40ZengBMCRespiratory Research1465-993X2023-08-0124111210.1186/s12931-023-02509-zIL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyteXiujuan Yao0Qinglin Chen1Xiangdong Wang2Xiaofang Liu3Luo Zhang4Department of Respiratory and Critical Care Medicine, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical UniversityAbstract Background Previous studies have shown that IL-25 levels are increased in patients with asthma with fixed airflow limitation (FAL). However, the mechanism by which IL-25 contributes to airway remodeling and FAL remains unclear. Here, we hypothesized that IL-25 facilitates pro-fibrotic phenotypic changes in bronchial epithelial cells (BECs) and circulating fibrocytes (CFs), orchestrates pathological crosstalk from BECs to CFs, and thereby contributes to airway remodeling and FAL. Methods Fibrocytes from asthmatic patients with FAL and chronic asthma murine models were detected using flow cytometry, multiplex staining and multispectral imaging analysis. The effect of IL-25 on BECs and CFs and on the crosstalk between BECs and CFs was determined using cell culture and co-culture systems. Results We found that asthmatic patients with FAL had higher numbers of IL-25 receptor (i.e., IL-17RB)+-CFs, which were negatively correlated with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). The number of airway IL-17RB+-fibrocytes was significantly increased in ovalbumin (OVA)- and IL-25-induced asthmatic mice versus the control subjects. BECs stimulated with IL-25 exhibited an epithelial-mesenchymal transition (EMT)-like phenotypic changes. CFs stimulated with IL-25 produced high levels of extracellular matrix (ECM) proteins and connective tissue growth factors (CTGF). These profibrotic effects of IL-25 were partially blocked by the PI3K-AKT inhibitor LY294002. In the cell co-culture system, OVA-challenged BECs facilitated the migration and expression of ECM proteins and CTGF in CFs, which were markedly blocked using an anti-IL-17RB antibody. Conclusion These results suggest that IL-25 may serve as a potential therapeutic target for asthmatic patients with FAL.https://doi.org/10.1186/s12931-023-02509-zAirway remodelingAsthmaBronchial epithelial cellsFibrocytesIL-25 |
| spellingShingle | Xiujuan Yao Qinglin Chen Xiangdong Wang Xiaofang Liu Luo Zhang IL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte Respiratory Research Airway remodeling Asthma Bronchial epithelial cells Fibrocytes IL-25 |
| title | IL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte |
| title_full | IL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte |
| title_fullStr | IL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte |
| title_full_unstemmed | IL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte |
| title_short | IL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte |
| title_sort | il 25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte |
| topic | Airway remodeling Asthma Bronchial epithelial cells Fibrocytes IL-25 |
| url | https://doi.org/10.1186/s12931-023-02509-z |
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