Natriuretic peptides as novel regulators of dendritic cells-mediated inflammation
Abstract Natriuretic Peptides (NPs), including atrial (ANP) and brain (BNP) types, exert pleiotropic effects in regulating immune responses via the Natriuretic Peptide Receptor-1 (NPR1), expressed across various immune cells. While NPs are established inhibitors of inflammasome activation and IL-1β...
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| Format: | Article |
| Language: | English |
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Springer
2025-07-01
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| Series: | Cellular and Molecular Life Sciences |
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| Online Access: | https://doi.org/10.1007/s00018-025-05769-8 |
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| author | Giorgia Manni Estevao Carlos Silva Barcelos Doriana Ricciuti Benedetta Pieroni Marco Gargaro Giulia Mencarelli Hans Acha-Orbea Vincenzo Nicola Talesa Letizia Mezzasoma Francesca Fallarino |
| author_facet | Giorgia Manni Estevao Carlos Silva Barcelos Doriana Ricciuti Benedetta Pieroni Marco Gargaro Giulia Mencarelli Hans Acha-Orbea Vincenzo Nicola Talesa Letizia Mezzasoma Francesca Fallarino |
| author_sort | Giorgia Manni |
| collection | DOAJ |
| description | Abstract Natriuretic Peptides (NPs), including atrial (ANP) and brain (BNP) types, exert pleiotropic effects in regulating immune responses via the Natriuretic Peptide Receptor-1 (NPR1), expressed across various immune cells. While NPs are established inhibitors of inflammasome activation and IL-1β secretion in human monocytes, their role in dendritic cells (DCs)-key regulators of innate and adaptive immunity-remains unclear. Inflammasome activation in DCs can yield both protective and detrimental outcomes depending on the context of the disease, suggesting that modulating this pathway could offer a promising pharmacological strategy for controlling immune responses. This study explored the regulation of the NLRP3 inflammasome by NPs in two conventional DC subsets: cDC1 and cDC2. We found that both subsets express basal levels of the NPR1 receptor, which increase under inflammatory conditions. Additionally, cDCs themselves produce ANP and BNP during inflammation. Although both subsets express basal levels of NLRP3 inflammasome proteins, cDC2 display a more robust NLRP3/IL-1β activation in response to LPS + ATP stimulation compared to cDC1. Notably, the NPs/NPR1 axis suppresses NLRP3 activation more effectively in the cDC2 subset by acting at translational and post-translational levels. These findings highlight NPs as a novel mechanism for controlling the inflammatory phenotype of cDCs and underscores NPs/NPR1 axis as therapeutic target for immune modulation of DC subsets. Graphical abstract cDC1 and cDC2 are equipped with the ANP/BNP–NPR1 axis and are sensitive to NLRP3 inflammasome activation. The natriuretic peptides ANP and BNP, through NPR1, represent a novel immunoregulatory mechanism that more effectively suppresses the inflammatory response in cDC2s than in cDC1. The NPs/NPR1 axis emerges as a potential therapeutic target for the control of pathological inflammation. Created in BioRender. https://BioRender.com/nrcr3m9 |
| format | Article |
| id | doaj-art-81b60cd4fb074622ac4f9264584f4bc0 |
| institution | Kabale University |
| issn | 1420-9071 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Cellular and Molecular Life Sciences |
| spelling | doaj-art-81b60cd4fb074622ac4f9264584f4bc02025-08-20T03:46:04ZengSpringerCellular and Molecular Life Sciences1420-90712025-07-0182111410.1007/s00018-025-05769-8Natriuretic peptides as novel regulators of dendritic cells-mediated inflammationGiorgia Manni0Estevao Carlos Silva Barcelos1Doriana Ricciuti2Benedetta Pieroni3Marco Gargaro4Giulia Mencarelli5Hans Acha-Orbea6Vincenzo Nicola Talesa7Letizia Mezzasoma8Francesca Fallarino9Department of Medicine and Surgery, University of PerugiaDepartment of Pharmaceutical Sciences, University of PerugiaDepartment of Medicine and Surgery, University of PerugiaDepartment of Medicine and Surgery, University of PerugiaDepartment of Pharmaceutical Sciences, University of PerugiaDepartment of Medicine and Surgery, University of PerugiaDepartment of Biochemistry CIIL, University of LausanneDepartment of Medicine and Surgery, University of PerugiaDepartment of Medicine and Surgery, University of PerugiaDepartment of Medicine and Surgery, University of PerugiaAbstract Natriuretic Peptides (NPs), including atrial (ANP) and brain (BNP) types, exert pleiotropic effects in regulating immune responses via the Natriuretic Peptide Receptor-1 (NPR1), expressed across various immune cells. While NPs are established inhibitors of inflammasome activation and IL-1β secretion in human monocytes, their role in dendritic cells (DCs)-key regulators of innate and adaptive immunity-remains unclear. Inflammasome activation in DCs can yield both protective and detrimental outcomes depending on the context of the disease, suggesting that modulating this pathway could offer a promising pharmacological strategy for controlling immune responses. This study explored the regulation of the NLRP3 inflammasome by NPs in two conventional DC subsets: cDC1 and cDC2. We found that both subsets express basal levels of the NPR1 receptor, which increase under inflammatory conditions. Additionally, cDCs themselves produce ANP and BNP during inflammation. Although both subsets express basal levels of NLRP3 inflammasome proteins, cDC2 display a more robust NLRP3/IL-1β activation in response to LPS + ATP stimulation compared to cDC1. Notably, the NPs/NPR1 axis suppresses NLRP3 activation more effectively in the cDC2 subset by acting at translational and post-translational levels. These findings highlight NPs as a novel mechanism for controlling the inflammatory phenotype of cDCs and underscores NPs/NPR1 axis as therapeutic target for immune modulation of DC subsets. Graphical abstract cDC1 and cDC2 are equipped with the ANP/BNP–NPR1 axis and are sensitive to NLRP3 inflammasome activation. The natriuretic peptides ANP and BNP, through NPR1, represent a novel immunoregulatory mechanism that more effectively suppresses the inflammatory response in cDC2s than in cDC1. The NPs/NPR1 axis emerges as a potential therapeutic target for the control of pathological inflammation. Created in BioRender. https://BioRender.com/nrcr3m9https://doi.org/10.1007/s00018-025-05769-8Cardiac hormonesAntigen presenting cellsAutoimmune diseasesInflammatory diseasesNatriuretic peptide receptor antagonistCytokines |
| spellingShingle | Giorgia Manni Estevao Carlos Silva Barcelos Doriana Ricciuti Benedetta Pieroni Marco Gargaro Giulia Mencarelli Hans Acha-Orbea Vincenzo Nicola Talesa Letizia Mezzasoma Francesca Fallarino Natriuretic peptides as novel regulators of dendritic cells-mediated inflammation Cellular and Molecular Life Sciences Cardiac hormones Antigen presenting cells Autoimmune diseases Inflammatory diseases Natriuretic peptide receptor antagonist Cytokines |
| title | Natriuretic peptides as novel regulators of dendritic cells-mediated inflammation |
| title_full | Natriuretic peptides as novel regulators of dendritic cells-mediated inflammation |
| title_fullStr | Natriuretic peptides as novel regulators of dendritic cells-mediated inflammation |
| title_full_unstemmed | Natriuretic peptides as novel regulators of dendritic cells-mediated inflammation |
| title_short | Natriuretic peptides as novel regulators of dendritic cells-mediated inflammation |
| title_sort | natriuretic peptides as novel regulators of dendritic cells mediated inflammation |
| topic | Cardiac hormones Antigen presenting cells Autoimmune diseases Inflammatory diseases Natriuretic peptide receptor antagonist Cytokines |
| url | https://doi.org/10.1007/s00018-025-05769-8 |
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