The presence of interleukin‐27 during monocyte‐derived dendritic cell differentiation promotes improved antigen processing and stimulation of T cells

• Published in: Immunology 2015-04, Vol.144 (4), p.649-660
• Main Authors: Jung, Joo‐Yong, Roberts, Lawton L., Robinson, Cory M.
• Format: Article
• Language: English
• Subjects: Antigen Presentation - drug effects; antigen‐presenting cell; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Coculture Techniques; dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - microbiology; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Humans; Hydrogen-Ion Concentration; Interleukin-12 - immunology; Interleukin-12 - metabolism; Interleukin-27 - pharmacology; interleukin‐27; Lymphocyte Activation - drug effects; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; Original; Phagosomes - drug effects; Phagosomes - immunology; Phagosomes - metabolism; Signal Transduction; Staphylococcus aureus - drug effects; Staphylococcus aureus - growth & development; Staphylococcus aureus - immunology; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - metabolism; Time Factors
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12417

Summary Dendritic cells (DCs) are potent antigen‐presenting cells necessary to establish effective adaptive immune responses. The cytokine environment that exists at the time of DC differentiation may be an important but often ignored determinant in the phenotypic and functional properties of DCs. Interleukin‐27 (IL‐27) is a unique cytokine that has both inflammatory and immune suppressive activities. Although it can both promote and oppose activity of different T‐cell subsets, mostly anti‐inflammatory activity has been described toward macrophages and DCs. However, the specific effect of IL‐27 during DC differentiation and how that may change the nature of the antigen‐presenting cell has not been investigated. In this report, we show that IL‐27 treatment during monocyte‐derived DC differentiation enhanced the ability to process antigens and stimulate T‐cell activity. DCs differentiated in the presence of IL‐27 showed enhanced acidification of latex bead‐containing phagosomes that was consistent with elevated expression of vacuolar‐ATPases. This resulted in inhibition of intracellular growth of Staphylococcus aureus. In addition, the levels of MHC class II surface expression were higher in DCs differentiated in the presence of IL‐27. Production of IL‐12 was also significantly increased during S. aureus infection of IL‐27‐differentiated DCs. The net effect of these activities was enhanced CD4+ T‐cell proliferation and T helper type 1 cytokine production. These findings are important to a wide number of immunological contexts and should be considered in the development of future vaccines.