Purified apoptotic bodies stimulate plasmacytoid dendritic cells to produce IFN-alpha

Background: Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFN). Human genome contains thirteen IFN alpha genes and one IFN beta gene. Research in mice suggests that different IFNs are induced by different stimuli, but whether this is true in human cells is unknown. Patients with HIV-1 infection show chronic interferon response in peripheral T cells, which caused us to analyze the induction of the IFN alpha genes in their dendritic cells. Methods: Uninfected, acutely infected and long-term non-progressive donors were leukopheresed, following which pDCs were isolated by negative depletion. The dendritic cells were then treated for with one of the following: influenza virus, sendai virus, HIV virus, CpG DNA, imiquimod, or media alone, and the cells’ RNA was analysed by real time qPCR for changes in the RNA levels of four IFN alpha genes: α1, α2, α7, α8, as well as IFN beta. Results: Final results were not available at the time of abstract deposition.

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Faculty Opinions recommendation of Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1024293.288736 ◽

2005 ◽

Author(s):

George Weiner

Keyword(s):

Dendritic Cells ◽

Plasmacytoid Dendritic Cells ◽

Short Interfering Rna ◽

Ifn Alpha ◽

Interfering Rna

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Faculty Opinions recommendation of Fc gamma RIIa is expressed on natural IFN-alpha-producing cells (plasmacytoid dendritic cells) and is required for the IFN-alpha production induced by apoptotic cells combined with lupus IgG.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1015525.197401 ◽

2003 ◽

Author(s):

Betty Tsao

Keyword(s):

Dendritic Cells ◽

Plasmacytoid Dendritic Cells ◽

Apoptotic Cells ◽

Ifn Alpha ◽

Alpha Production

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TSG-6 Downregulates IFN-Alpha and TNF-Alpha Expression by Suppressing IRF7 Phosphorylation in Human Plasmacytoid Dendritic Cells

Mediators of Inflammation ◽

10.1155/2017/7462945 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

L. Kui ◽

G. C. Chan ◽

P. P. W. Lee

Keyword(s):

Dendritic Cells ◽

Lupus Erythematosus ◽

Proinflammatory Cytokine ◽

Suppressive Effect ◽

Plasmacytoid Dendritic Cells ◽

Type I Interferons ◽

Type I ◽

Ifn Alpha ◽

Healthy Donors

Proinflammatory cytokines such as TNF-α and type I interferons (IFN) are pathogenic signatures of systemic lupus erythematosus, and plasmacytoid dendritic cells (pDCs) play a major role by predominantly producing IFN-α. Given the rise of importance in identifying tumor necrosis stimulated gene 6 (TSG-6) as a key anti-inflammatory regulator, we investigate its function and its ability to counteract proinflammatory cytokine secretion by pDCs in vitro. CpG-A and R837 induced significant endogenous TSG-6 expression in the pDC cell-line GEN2.2. Following recombinant human TSG-6 treatment and CpG-A or R837 stimulation, significant reduction in IFN-α and TNF-α was observed in healthy donors’ pDCs, and the same phenomenon was confirmed in GEN2.2. By CD44 blocking assay, we deduced that the suppressive effect of TSG-6 is mediated by CD44, by reducing IRF-7 phosphorylation. Our findings suggest that TSG-6 and its downstream signalling pathway could potentially be targeted to modulate proinflammatory cytokine expression in pDCs.

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