title: Synergistic production of TNFα and IFNα by human pDCs incubated with IFNλ3 and IL-3.
abstract: In this study, we investigated whether IFNλ3 and IL-3 reciprocally influence their capacity to activate various functions of human plasmacytoid dendritic cells (pDCs). In fact, we preliminarily observed that IFNλ3 upregulates the expression of the IL-3Rα (CD123), while IL-3 augments the expression of IFNλR1 in pDCs. As a result, we found that combination of IFNλ3 and IL-3 induces a strong potentiation in the production of TNFα, IFNα, as well as in the expression of Interferon-Stimulated Gene (ISG) mRNAs by pDCs, as compared to either IFNλ3 or IL-3 alone. In such regard, we found that endogenous IFNα autocrinally promotes the expression of ISG mRNAs in IL-3-, but not in IFNλ3 plus IL-3-, treated pDCs. Moreover, we uncovered that the production of IFNα by IFNλ3 plus IL-3-treated pDCs is mostly dependent on endogenously produced TNFα. Altogether, our data demonstrate that IFNλ3 and IL-3 collaborate to promote, at maximal levels, discrete functional responses of human pDCs.
authors: Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
authors: Giulia
authors: G
authors: Finotti
authors: Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
authors: Nicola
authors: N
authors: Tamassia
authors: Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy. Electronic address: marco.cassatella@univr.it.
authors: Marco A
authors: MA
authors: Cassatella
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000276:immunology; D007372:Interferons; D007377:Interleukin-3 / Q000494:pharmacology*; D053650:Interleukin-3 Receptor alpha Subunit / Q000235:genetics; D007378:Interleukins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology; D015854:Up-Regulation; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D007377:Interleukin-3; D053650:Interleukin-3 Receptor alpha Subunit; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C115022:IL3RA protein, human
keywords: IL-3; innate immunity; interferon lambda; plasmacytoid dendritic cells