ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
Regulatory role of SphK1 in TLR7/9-dependent type I interferon response and autoimmunity.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- Machine learning models to identify lead compound and substitution optimization to have derived energetics and conformational stability through docking and MD simulations for sphingosine kinase 1.Molecular diversity · 2025Article
- Targeting acid ceramidase enhances antitumor immune response in colorectal cancer.Journal of advanced research · 2024Article
- Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?International journal of molecular sciences · 2023Review
- Sphingosine 1-Phosphate as Essential Signaling Molecule in Inflammatory Skin Diseases.International journal of molecular sciences · 2023Review
- The role of sphingosine-1-phosphate in the gut mucosal microenvironment and inflammatory bowel diseases.Frontiers in physiology · 2023Review
- The Impact of Sphingosine Kinases on Inflammation-Induced Cytokine Release and Vascular Endothelial Barrier Integrity.International journal of molecular sciences · 2022Article
- Inhibition of SphK1/S1P Signaling Pathway Alleviates Fibrosis and Inflammation of Rat Myocardium after Myocardial Infarction.Computational and mathematical methods in medicine · 2022Article
- Type I Interferon Production of Plasmacytoid Dendritic Cells under Control.International journal of molecular sciences · 2021Review
- Therapeutic Potential of SphK1 Inhibitors Based on Abnormal Expression of SphK1 in Inflammatory Immune Related-Diseases.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
Plasmacytoid dendritic cells (pDCs) express Toll like receptors (TLRs) that modulate the immune response by production of type I interferons. Here, we report that sphingosine kinase 1 (SphK1) which produces the bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P), plays a critical role in the pDC functions and interferon production. Although dispensable for the pDC development, SphK1 is essential for the pDC activation and production of type I IFN and pro-inflammatory cytokines stimulated by TLR7/9 ligands. SphK1 interacts with TLRs and specific inhibition or deletion of SphK1 in pDCs mitigates uptake of CpG oligonucleotide ligands by TLR9 ligand. In the pristane-induced murine lupus model, pharmacological inhibition of SphK1 or its genetic deletion markedly decreased the IFN signature, pDC activation, and glomerulonephritis. Moreover, increases in the SphK1 expression and S1P levels were observed in human lupus patients. Taken together, our results indicate a pivotal regulatory role for the SphK1/S1P axis in maintaining the balance between immunosurveillance and immunopathology and suggest that specific SphK1 inhibitors might be a new therapeutic avenue for the treatment of type I IFN-linked autoimmune disorders.
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Registered trials
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