ArticleArthritis research & therapy2018
Cytokine production by activated plasmacytoid dendritic cells and natural killer cells is suppressed by an IRAK4 inhibitor.
Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Effects of Hydroxychloroquine on Proteinuria in IgA Nephropathy: A Systematic Review and Meta-Analysis.BioMed research international · 2021Pooled it
- The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell Resolution.Frontiers in immunology · 2021Trial
- Plasmacytoid dendritic cells alleviate atopic dermatitis by suppressing Th2 inflammation via the IFN-α/IFNAR1 pathway.Frontiers in immunology · 2026Article
- Immunopathogenesis of Systemic Lupus Erythematosus: Interplay of Innate and Adaptive Immunity, Microbiome Dysbiosis, and Emerging Therapeutic Targets.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Review
- Expression pattern and clinical significance of MerTK on circulating NK cells in systemic lupus erythematosus.Lupus science & medicine · 2025Article
- Mechanism and target treatment of primary immunodeficiency diseases with systemic lupus erythematosus-like phenotype.Pediatric discovery · 2024Review
- Deciphering the immunological interactions: targeting preeclampsia with Hydroxychloroquine's biological mechanisms.Frontiers in pharmacology · 2024Review
- Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus.Medicina (Kaunas, Lithuania) · 2023Article
- Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus.International journal of molecular sciences · 2023Review
- Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus.Frontiers in immunology · 2023Review
- Mucosal Immunity and the Gut-Microbiota-Brain-Axis in Neuroimmune Disease.International journal of molecular sciences · 2022Review
- IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies.Current opinion in hematology · 2022Review
- Mechanisms of Immunothrombosis by SARS-CoV-2.Biomolecules · 2021Review
- SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4.The Journal of experimental medicine · 2021Article
- 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 signalling in B cells during systemic lupus erythematosus.Nature reviews. Rheumatology · 2021Review
- SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4.bioRxiv : the preprint server for biology · 2021Article
- The Therapeutic Landscape of Rheumatoid Arthritis: Current State and Future Directions.Frontiers in pharmacology · 2021Review
- Short-term high-dose gavage of hydroxychloroquine changes gut microbiota but not the intestinal integrity and immunological responses in mice.Life sciences · 2021Article
- Natural killer cells in inflammatory autoimmune diseases.Clinical & translational immunology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn systemic lupus erythematosus (SLE), immune complexes (ICs) containing self-derived nucleic acids trigger the synthesis of proinflammatory cytokines by immune cells. We asked how an interleukin (IL)-1 receptor-associated kinase 4 small molecule inhibitor (IRAK4i) affects RNA-IC-induced cytokine production compared with hydroxychloroquine (HCQ).
methodsPlasmacytoid dendritic cells (pDCs) and natural killer (NK) cells were isolated from peripheral blood mononuclear cells (PBMCs) of healthy individuals. PBMCs from SLE patients and healthy individuals were depleted of monocytes. Cells were stimulated with RNA-containing IC (RNA-IC) in the presence or absence of IRAK4i I92 or HCQ, and cytokines were measured by immunoassay or flow cytometry. Transcriptome sequencing was performed on RNA-IC-stimulated pDCs from healthy individuals to assess the effect of IRAK4i and HCQ.
resultsIn healthy individuals, RNA-IC induced interferon (IFN)-α, tumor necrosis factor (TNF)-α, IL-6, IL-8, IFN-γ, macrophage inflammatory protein (MIP)1-α, and MIP1-β production in pDC and NK cell cocultures. IFN-α production was selective for pDCs, whereas both pDCs and NK cells produced TNF-α. IRAK4i reduced the pDC and NK cell-derived cytokine production by 74-95%. HCQ interfered with cytokine production in pDCs but not in NK cells. In monocyte-depleted PBMCs, IRAK4i blocked cytokine production more efficiently than HCQ. Following RNA-IC activation of pDCs, 975 differentially expressed genes were observed (false discovery rate (FDR) < 0.05), with many connected to cytokine pathways, cell regulation, and apoptosis. IRAK4i altered the expression of a larger number of RNA-IC-induced genes than did HCQ (492 versus 65 genes).
conclusionsThe IRAK4i I92 exhibits a broader inhibitory effect than HCQ on proinflammatory pathways triggered by RNA-IC, suggesting IRAK4 inhibition as a therapeutic option in SLE.
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