ArticleScientific reports2017
Serotonin drives the acquisition of a profibrotic and anti-inflammatory gene profile through the 5-HT7R-PKA signaling axis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 68 citations in OpenAlex.
- Review
- Review
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- The neuro-immune axis in cancer: from mechanisms to therapeutic opportunities.Journal of hematology & oncology · 2025Review
- Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HTActa neuropsychiatrica · 2025Review
- 5-HTJournal of advanced research · 2025Article
- Serotonin receptor 5-HT7 modulates inflammatory-associated functions of macrophages.Cellular and molecular life sciences : CMLS · 2025Article
- Single-Nuclei Transcriptome Profiling Reveals Intra-Tumoral Heterogeneity and Characterizes Tumor Microenvironment Architecture in a Murine Melanoma Model.International journal of molecular sciences · 2024Article
- Neuroimmune Crossroads: The Interplay of the Enteric Nervous System and Intestinal Macrophages in Gut Homeostasis and Disease.Biomolecules · 2024Review
- Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities.Clinical and translational medicine · 2024Review
- Serotonin Receptors in Myocardial Infarction: Friend or Foe?ACS chemical neuroscience · 2024Review
- Role of Serotonergic System in Regulating Brain Tumor-Associated Neuroinflammatory Responses.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Can Serotonin 7 Receptors Be a Treatment Target for Noncentral Diseases?The Eurasian journal of medicine · 2023Article
- Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease.Nature communications · 2023Article
- Targeting the brain 5-HT7 receptor to prevent hypomyelination in a rodent model of perinatal white matter injuries.Journal of neural transmission (Vienna, Austria : 1996) · 2023Article
- Vancomycin-induced gut microbial dysbiosis alters enteric neuron-macrophage interactions during a critical period of postnatal development.Frontiers in immunology · 2023Article
- Macrophages and platelets in liver fibrosis and hepatocellular carcinoma.Frontiers in immunology · 2023Review
- The role of macrophage subtypes and exosomes in immunomodulation.Cellular & molecular biology letters · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peripheral serotonin (5-hydroxytryptamine, 5-HT) regulates cell growth and differentiation in numerous cell types through engagement of seven types of cell surface receptors (HTR1-7). Deregulated 5-HT/HTR levels contribute to pathology in chronic inflammatory diseases, with macrophages being relevant targets for the physio-pathological effects of 5-HT. In fact, 5-HT skews human macrophage polarization through engagement of 5-HT2BR and 5-HT7R receptors. We now report that 5-HT primes macrophages for reduced pro-inflammatory cytokine production and IFN type I-mediated signaling, and promotes an anti-inflammatory and pro-fibrotic gene signature in human macrophages. The acquisition of the 5-HT-dependent gene profile primarily depends on the 5-HT7R receptor and 5-HT7R-initiated PKA-dependent signaling. In line with the transcriptional results, 5-HT upregulates TGFβ1 production by human macrophages in an HTR7- and PKA-dependent manner, whereas the absence of Htr7 in vivo results in diminished macrophage infiltration and collagen deposition in a mouse model of skin fibrosis. Our results indicate that the anti-inflammatory and pro-fibrotic activity of 5-HT is primarily mediated through the 5-HT7R-PKA axis, and that 5-HT7R contributes to pathology in fibrotic diseases.
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