Promoting ER stress in a plasmacytoid dendritic cell line drives fibroblast activation
Abstract Background Fibrosis remains a major complication in several chronic diseases, including systemic sclerosis (SSc). Plasmacytoid dendritic cells (pDCs) are innate immune cells that play a key role in the development of fibrosis in SSc patients, through still poorly defined mechanisms. Interes...
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BMC
2025-02-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02057-7 |
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| author | Beatriz H. Ferreira Inês S. Silva Andreia Mendes Fátima Leite-Pinheiro Adrienne W. Paton James C. Paton Iola F. Duarte Philippe Pierre Catarina R. Almeida |
| author_facet | Beatriz H. Ferreira Inês S. Silva Andreia Mendes Fátima Leite-Pinheiro Adrienne W. Paton James C. Paton Iola F. Duarte Philippe Pierre Catarina R. Almeida |
| author_sort | Beatriz H. Ferreira |
| collection | DOAJ |
| description | Abstract Background Fibrosis remains a major complication in several chronic diseases, including systemic sclerosis (SSc). Plasmacytoid dendritic cells (pDCs) are innate immune cells that play a key role in the development of fibrosis in SSc patients, through still poorly defined mechanisms. Interestingly, endoplasmic reticulum (ER) stress signaling pathways are dysregulated in pDCs from patients with SSc, but their contribution to fibrosis remains unclear. Thus, this study aimed to unravel the mechanisms behind the involvement of pDCs and ER stress in fibrosis. Methods To address this question, we established an in vitro model designed to study the interactions between pDCs and fibroblasts. More specifically, IMR-90 fibroblasts were co-cultured with CAL-1, a pDC cell line. ER stress was then induced by the bacterial toxin SubAB. Extracellular matrix (ECM) production was assessed using immunoblotting, qPCR and confocal microscopy. The importance of cell-to-cell contact was investigated using conditioned media (CM) and transwell assays. Results Direct contact of CAL-1 and IMR-90 cells under ER stress conditions led to increased expression of fibronectin and alpha-smooth muscle actin (α-SMA). This effect required expression of the ER stress signaling sensor protein kinase R-like ER kinase (PERK) in pDCs and was observed only upon direct contact between both cell types. Conclusions Overall, our data suggest that ER stress induction in pDCs promotes fibroblast activation, which may contribute to the development of fibrosis in SSc. |
| format | Article |
| id | doaj-art-26e4e5209d32496eb4fac2dce97bca8a |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-26e4e5209d32496eb4fac2dce97bca8a2025-02-09T12:47:25ZengBMCCell Communication and Signaling1478-811X2025-02-0123111210.1186/s12964-025-02057-7Promoting ER stress in a plasmacytoid dendritic cell line drives fibroblast activationBeatriz H. Ferreira0Inês S. Silva1Andreia Mendes2Fátima Leite-Pinheiro3Adrienne W. Paton4James C. Paton5Iola F. Duarte6Philippe Pierre7Catarina R. Almeida8Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of AveiroInstitute of Biomedicine (iBiMED), Department of Medical Sciences, University of AveiroInstitute of Biomedicine (iBiMED), Department of Medical Sciences, University of AveiroInstitute of Biomedicine (iBiMED), Department of Medical Sciences, University of AveiroDepartment of Molecular and Biomedical Science, Research Centre for Infectious Diseases, University of AdelaideDepartment of Molecular and Biomedical Science, Research Centre for Infectious Diseases, University of AdelaideCICECO - Aveiro Institute of Materials, Department of Chemistry, University of AveiroInstitute of Biomedicine (iBiMED), Department of Medical Sciences, University of AveiroInstitute of Biomedicine (iBiMED), Department of Medical Sciences, University of AveiroAbstract Background Fibrosis remains a major complication in several chronic diseases, including systemic sclerosis (SSc). Plasmacytoid dendritic cells (pDCs) are innate immune cells that play a key role in the development of fibrosis in SSc patients, through still poorly defined mechanisms. Interestingly, endoplasmic reticulum (ER) stress signaling pathways are dysregulated in pDCs from patients with SSc, but their contribution to fibrosis remains unclear. Thus, this study aimed to unravel the mechanisms behind the involvement of pDCs and ER stress in fibrosis. Methods To address this question, we established an in vitro model designed to study the interactions between pDCs and fibroblasts. More specifically, IMR-90 fibroblasts were co-cultured with CAL-1, a pDC cell line. ER stress was then induced by the bacterial toxin SubAB. Extracellular matrix (ECM) production was assessed using immunoblotting, qPCR and confocal microscopy. The importance of cell-to-cell contact was investigated using conditioned media (CM) and transwell assays. Results Direct contact of CAL-1 and IMR-90 cells under ER stress conditions led to increased expression of fibronectin and alpha-smooth muscle actin (α-SMA). This effect required expression of the ER stress signaling sensor protein kinase R-like ER kinase (PERK) in pDCs and was observed only upon direct contact between both cell types. Conclusions Overall, our data suggest that ER stress induction in pDCs promotes fibroblast activation, which may contribute to the development of fibrosis in SSc.https://doi.org/10.1186/s12964-025-02057-7UPRPERKCell-cell communicationFibrosisPlasmacytoid dendritic cellsFibroblasts |
| spellingShingle | Beatriz H. Ferreira Inês S. Silva Andreia Mendes Fátima Leite-Pinheiro Adrienne W. Paton James C. Paton Iola F. Duarte Philippe Pierre Catarina R. Almeida Promoting ER stress in a plasmacytoid dendritic cell line drives fibroblast activation Cell Communication and Signaling UPR PERK Cell-cell communication Fibrosis Plasmacytoid dendritic cells Fibroblasts |
| title | Promoting ER stress in a plasmacytoid dendritic cell line drives fibroblast activation |
| title_full | Promoting ER stress in a plasmacytoid dendritic cell line drives fibroblast activation |
| title_fullStr | Promoting ER stress in a plasmacytoid dendritic cell line drives fibroblast activation |
| title_full_unstemmed | Promoting ER stress in a plasmacytoid dendritic cell line drives fibroblast activation |
| title_short | Promoting ER stress in a plasmacytoid dendritic cell line drives fibroblast activation |
| title_sort | promoting er stress in a plasmacytoid dendritic cell line drives fibroblast activation |
| topic | UPR PERK Cell-cell communication Fibrosis Plasmacytoid dendritic cells Fibroblasts |
| url | https://doi.org/10.1186/s12964-025-02057-7 |
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