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Series GSE149415 Query DataSets for GSE149415
Status Public on May 23, 2020
Title The regulation and pharmacological modulation of immune complex induced type III IFN production by plasmacytoid dendritic cells [microarray]
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Objective: Patients 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 interferon (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. Methods: Peripheral 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. Results: Type 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%. Conclusions: Type 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.
Overall design RNA was isolated after 6 hours treatment of cells from two healthy individuals with RNA-IC or medium (mock).
Contributor(s) Hjorton K, Hagberg N, Pucholt P, Eloranta M, Rönnblom L
Citation(s) 32503683
Submission date Apr 27, 2020
Last update date Jun 16, 2020
Contact name Pascal Pucholt
Organization name Uppsala University
Department Medical Science
Lab Rheumatology
Street address Dag Hammarskjölds väg 20
City Uppsala
ZIP/Postal code 751 23
Country Sweden
Platforms (1)
GPL13607 Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version)
Samples (20)
GSM4500789 pDC_mock_indA
GSM4500790 pDC_IC_indA
GSM4500791 B_mock_indA
This SubSeries is part of SuperSeries:
GSE149456 The regulation and pharmacological modulation of immune complex induced type III IFN production by plasmacytoid dendritic cells
BioProject PRJNA628646

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE149415_RAW.tar 248.9 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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