ArticlePloS one2016
Dual Role of the Tyrosine Kinase Syk in Regulation of Toll-Like Receptor Signaling in Plasmacytoid Dendritic Cells.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
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- Interferon-directed therapies for the treatment of systemic lupus erythematosus: a critical update.Clinical rheumatology · 2021Review
- Characterization of the mechanism of action of lanraplenib, a novel spleen tyrosine kinase inhibitor, in models of lupus nephritis.BMC rheumatology · 2021Article
- Toll-like receptor dual-acting agonists are potent inducers of PBMC-produced cytokines that inhibit hepatitis B virus production in primary human hepatocytes.Scientific reports · 2020Article
- The role of Toll-like receptor signaling pathways in cerebrovascular disorders: the impact of spreading depolarization.Journal of neuroinflammation · 2020Review
- Role of spleen tyrosine kinase in liver diseases.World journal of gastroenterology · 2020Review
- Endosomal toll-like receptors play a key role in activation of primary human monocytes by cowpea mosaic virus.Immunology · 2020Article
- Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling.Frontiers in immunology · 2020Article
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- Therapeutic Implication of SOCS1 Modulation in the Treatment of Autoimmunity and Cancer.Frontiers in pharmacology · 2019Review
- Tyrosine kinase SYK is a potential therapeutic target for liver fibrosis.Hepatology (Baltimore, Md.) · 2018Article
- Expression of TIM-3 on Plasmacytoid Dendritic Cells as a Predictive Biomarker of Decline in HIV-1 RNA Level during ART.Viruses · 2018Article
- Viruses Seen by Our Cells: The Role of Viral RNA Sensors.Journal of immunology research · 2018Review
- The MEK1/2-ERK Pathway Inhibits Type I IFN Production in Plasmacytoid Dendritic Cells.Frontiers in immunology · 2018Article
- FcγRIIIa Signaling Modulates Endosomal TLR Responses in Human CD4Journal of immunology (Baltimore, Md. : 1950) · 2017Article
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- Proteomic Analysis of HDAC3 Selective Inhibitor in the Regulation of Inflammatory Response of Primary Microglia.Neural plasticity · 2017Article
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crosslinking of regulatory immunoreceptors (RR), such as BDCA-2 (CD303) or ILT7 (CD85g), of plasmacytoid dendritic cells (pDCs) efficiently suppresses production of type-I interferon (IFN)-α/β and other cytokines in response to Toll-like receptor (TLR) 7/9 ligands. This cytokine-inhibitory pathway is mediated by spleen tyrosine kinase (Syk) associated with the ITAM-containing adapter of RR. Here we demonstrate by pharmacological targeting of Syk that in addition to the negative regulation of TLR7/9 signaling via RR, Syk also positively regulates the TLR7/9 pathway in human pDCs. Novel highly specific Syk inhibitor AB8779 suppressed IFN-α, TNF-α and IL-6 production induced by TLR7/9 agonists in primary pDCs and in the pDC cell line GEN2.2. Triggering of TLR9 or RR signaling induced a differential kinetics of phosphorylation at Y352 and Y525/526 of Syk and a differential sensitivity to AB8779. Consistent with the different roles of Syk in TLR7/9 and RR signaling, a concentration of AB8779 insufficient to block TLR7/9 signaling still released the block of IFN-α production triggered via the RR pathway, including that induced by hepatitis B and C viruses. Thus, pharmacological targeting of Syk partially restored the main pDC function-IFN-α production. Opposing roles of Syk in TLR7/9 and RR pathways may regulate the innate immune response to weaken inflammation reaction.
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