Synergistic production of TNFα and IFNα by human pDCs incubated with IFNλ3 and IL-3 |
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Institution: | 1. Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran;2. Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran;3. Research Centre for Emerging and Reemerging infectious diseases, Pasteur Institute of Iran, Tehran, Iran;4. Department of Epidemiology and Biostatistics, Pasteur Institute of Iran, Tehran, Iran;5. Department of Microbiology and Immunology, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran;1. Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA;2. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA;3. Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA, USA;4. Department of Pharmacology and Experimental Neuroscience, Omaha, NE 68105, USA |
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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. |
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Keywords: | plasmacytoid dendritic cells interferon lambda IL-3 innate immunity |
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