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Plasmacytoid Dendritic Cells both produce interferon‐λ and respond to interferon‐λ stimulation
Author(s) -
Yin Zhiwei,
Amrute Sheela,
Lewisantes Anita,
Donnelly Raymond P.,
Kotenko Serguei,
Bocarsly Patricia F.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1070.23
Subject(s) - interferon , tlr9 , autocrine signalling , cytokine , sendai virus , stimulation , receptor , biology , tlr7 , flow cytometry , downregulation and upregulation , microbiology and biotechnology , immunology , virus , innate immune system , toll like receptor , gene expression , gene , endocrinology , biochemistry , dna methylation
PDC are considered to be “professional” type I IFN producing cells in that they produce 10–100‐fold more IFN‐α in response to enveloped viruses than other cell types. We investigated the ability of human PDC to produce and respond to IFN‐λ (IL‐28/‐29). We developed an intracellular flow cytometry assay to assess the expression of IFN‐λ protein. A subset of IFN‐α + PDC was found to express IFN‐λ after stimulation with HSV, flu, Sendai virus, as well as with TLR9 and ‐7 agonists, with IFN‐λ expressed by those cells with the highest IFN‐α expression. As we previously reported for IFN‐α, cross‐linking of CD4 on PDC inhibited HSV‐induced IFN‐λ production. Also as with IFN‐α, HSV‐induced IFN‐λ production in PDC was mediated through TLR9. By ELISA, PDC produced ~10‐fold more IFN‐α than –λ. Both unstimulated and stimulated PDC were found to express high levels of IFN‐λ receptor mRNA and stimulated PDC expressed both IFN‐λ1 (IL‐29) and –λ2 (IL‐28) mRNA. IFN‐λ treatment of PDC led to upregulation of the expression of both IFN‐α and IFN‐λ protein. In addition, exogenous IFN‐λ inhibited apoptosis of PDC. We conclude that PDC are major producers of IFN‐λ in response to viral stimulation and also express receptors for this cytokine. Moreover, these receptors are functional in that IFN‐λ has autocrine effects that strengthen the antiviral activity of the PDC by increasing both IFN‐α and IFN‐λ production and promoting PDC survival. (AI26806).