ArticlePloS one2015
Type I interferon-mediated skewing of the serotonin synthesis is associated with severe disease in systemic lupus erythematosus.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- Pooled it
- A systematic review and meta-analysis of the kynurenine pathway of tryptophan metabolism in rheumatic diseases.Frontiers in immunology · 2023Pooled it
- Interferon-Driven Tryptophan Metabolism Links Inflammation and Mental Health in Juvenile Dermatomyositis.Inflammation · 2026Article
- Neurotransmitters as regulators of autoimmunity: mechanisms and translational targeting.NPJ autoimmunity · 2026Review
- IFNγ-associated immune-metabolic remodeling is linked to serotonin-kynurenine imbalance and cortical vulnerability in lupus-prone mice.Frontiers in immunology · 2026Article
- Diffuse neuropsychiatric lupus: Clinical evidence, immune-mediated mechanisms, and therapeutic insights.Seminars in immunology · 2025Review
- Neuropsychiatric manifestations in systemic lupus erythematosus and Sjogren's disease.Autoimmunity reviews · 2025Review
- Platelet Ido1 expression is induced during Plasmodium yoelii infection, altering plasma tryptophan metabolites.Blood advances · 2024Article
- Tissue Kallikrein-1 Suppresses Type I Interferon Responses and Reduces Depressive-Like Behavior in the MRL/lpr Lupus-Prone Mouse Model.International journal of molecular sciences · 2024Article
- How Protein Depletion Balances Thrombosis and Bleeding Risk in the Context of Platelet's Activatory and Negative Signaling.International journal of molecular sciences · 2024Review
- Intersection of the microbiome and immune metabolism in lupus.Immunological reviews · 2024Review
- Tryptophan degradation as a systems phenomenon in inflammation - an analysis across 13 chronic inflammatory diseases.EBioMedicine · 2024Article
- From intestinal metabolites to the brain: Investigating the mysteries of Long COVID.Clinical and translational medicine · 2024Article
- Dietary tryptophan and genetic susceptibility expand gut microbiota that promote systemic autoimmune activation.bioRxiv : the preprint server for biology · 2024Article
- Article
- Associations between circulating interferon and kynurenine/tryptophan pathway metabolites: support for a novel potential mechanism for cognitive dysfunction in SLE.Lupus science & medicine · 2022Article
- Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the Proteome of Platelets from Patients with Systemic Lupus Erythematosus.Thrombosis and haemostasis · 2022Article
- Article
- Arenaviral infection causes bleeding in mice due to reduced serotonin release from platelets.Science signaling · 2022Article
- The Role of Diet in Influencing the Diversity of Gut Microbiome Related to Lupus Disease Activities: A Systematic Review.International journal of microbiology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serotonin, a highly pro-inflammatory molecule released by activated platelets, is formed by tryptophan. Tryptophan is also needed in the production of kynurenine, a process mediated by the type I interferon (IFN)-regulated rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO). The aim of this study was to investigate levels of serotonin in patients with the autoimmune disease systemic lupus erythematosus (SLE), association to clinical phenotype and possible involvement of IDO in regulation of serotonin synthesis. Serotonin levels were measured in serum and plasma from patients with SLE (n=148) and healthy volunteers (n=79) by liquid chromatography and ELISA, as well as intracellularly in platelets by flow cytometry. We found that SLE patients had decreased serotonin levels in serum (p=0.01) and platelets (p<0.0001) as compared to healthy individuals. SLE patients with ongoing type I IFN activity, as determined by an in-house reporter assay, had decreased serum levels of serotonin (p=0.0008) as well as increased IDO activity (p<0.0001), as determined by the kynurenine/tryptophan ratio measured by liquid chromatography. Furthermore, SLE sera induced IDO expression in WISH cells in a type I IFN-dependent manner (p=0.008). Also platelet activation contributed to reduce overall availability of serotonin levels in platelets and serum (p<0.05). Decreased serum serotonin levels were associated with severe SLE with presence of anti-dsDNA antibodies and nephritis. In all, reduced serum serotonin levels in SLE patients were related to severe disease phenotype, including nephritis, suggesting involvement of important immunopathological processes. Further, our data suggest that type I IFNs, present in SLE sera, are able to up-regulate IDO expression, which may lead to decreased serum serotonin levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.