ArticleArthritis research & therapy2020
The regulation and pharmacological modulation of immune complex induced type III IFN production by plasmacytoid dendritic cells.
Article in Arthritis research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Systemic lupus erythematosus: from an adverse event of interferon administration to a disease with new treatment options.Upsala journal of medical sciences · 2025Review
- Focus on Interferon Signature in Cutaneous Lupus Erythematosus: Novel Therapies From Better Understanding of the Pathogenesis.Journal of immunology research · 2025Review
- CSL362 potently and specifically depletes pDCsiScience · 2023Article
- Article
- Single-Cell Sequencing in Rheumatic Diseases: New Insights from the Perspective of the Cell Type.Aging and disease · 2022Article
- Impact of single-cell RNA sequencing on understanding immune regulation.Journal of cellular and molecular medicine · 2022Review
- Rebooting Regulatory T Cell and Dendritic Cell Function in Immune-Mediated Inflammatory Diseases: Biomarker and Therapy Discovery under a Multi-Omics Lens.Biomedicines · 2022Review
- B Cell Activation and Plasma Cell Differentiation Are Promoted by IFN-λ in Systemic Lupus Erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- The Pathogenesis, Molecular Mechanisms, and Therapeutic Potential of the Interferon Pathway in Systemic Lupus Erythematosus and Other Autoimmune Diseases.International journal of molecular sciences · 2021Review
- Interferon lambda in inflammation and autoimmune rheumatic diseases.Nature reviews. Rheumatology · 2021Review
- Single Cell RNA Sequencing in Autoimmune Inflammatory Rheumatic Diseases: Current Applications, Challenges and a Step Toward Precision Medicine.Frontiers in medicine · 2021Review
- Comparison of Surrogate Markers of the Type I Interferon Response and Their Ability to Mirror Disease Activity in Systemic Lupus Erythematosus.Frontiers in immunology · 2021Article
- Phenotypical Diversification of Early IFNα-Producing Human Plasmacytoid Dendritic Cells Using Droplet-Based Microfluidics.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivePatients with systemic lupus erythematosus (SLE) have an ongoing interferon (IFN) production due to an activation of plasmacytoid dendritic cells (pDCs), which can be triggered to type I IFN synthesis by RNA containing immune complexes (RNA-IC). Considering emerging data suggesting a role of type III IFN in the SLE disease process, we asked if RNA-IC can induce type III IFN production in pDC and how this production can be regulated.
methodsPeripheral blood mononuclear cells (PBMCs) or immune cell subsets were isolated from healthy blood donors or SLE patients and stimulated with IC containing U1 snRNP and SLE-IgG (RNA-IC). Hydroxychloroquine (HCQ) and an interleukin receptor 1-associated kinase 4 inhibitor (IRAK4i) were added to cell cultures. Cytokine mRNA levels were determined with a microarray and protein levels with immunoassays. Single-cell RNA sequencing of pDCs using ddSEQ technology was performed.
resultsType III IFN mRNA and protein was induced in RNA-IC-stimulated pDC-NK and pDC-B cell co-cultures. A subset of activated pDCs (3%) expressed both type III and type I IFN mRNA. IFN-λ2, IFN-α2b, interleukin (IL)-3, IL-6, or granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced IFN-λ1/3 production 2-5-fold. HCQ and an IRAK4i blocked the RNA-IC-triggered IFN-λ1/3 production (p < 0.01). IFN-α2b and GM-CSF increased the proportion of SLE patients producing IFN-λ1/3 in response to RNA-IC from 11 to 33%.
conclusionsType III IFN production is triggered by RNA-IC in pDCs in a TLR-MyD88-dependent manner, enhanced by NK and B cells as well as several pro-inflammatory cytokines. These results support a contributing role for both type I and type III IFNs in SLE, which needs to be considered when targeting the IFN system in this disease.
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