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

Abstract

SummaryDendritic 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.

Autoimmune Regulator Expression in DC2.4 Cells Regulates the NF-κB Signaling and Cytokine Expression of the Toll-Like Receptor 3 Pathway

“…IL-27 stimulation can significantly improve Treg function both in vitro and in vivo. Type I IFN can also induce Treg phenotype polarization [15,16,17,18]. In this study, we observed the increases of IL-27 and IFN expression in untreated GFP-Aire/DC.…”

Patterns, Receptors, and Signals: Regulation of Phagosome Maturation

“…By contrast, short-term stimulation of MΦs with IL-4 delayed the acquisition of phagosome maturation markers and phagosomal acidification after uptake of immunoglobulin G (IgG)-opsonized zymosan [44]. Moreover, stimulation of DCs with IL-27 for several days induced enhanced phagosomal acidification, as measured by increased co-localization of phagosomes with lysotracker, and enhanced acquisition of proteolytic enzymes, such as cathepsin D [45]. By contrast, stimulation of DCs with TNF and CD40 ligand did not induce major differences in phagosomal degradation [36].…”

Murine myeloid‐derived suppressor cells are a source of elevated levels of interleukin‐27 in early life and compromise control of bacterial infection

“…5,6 IL-27 was first identified for its role in differentiation of na€ ıve T cells to a Th1 phenotype and the ability to augment IL-12-induced IFN-c production. 6,7 Although inflammatory activity toward human monocytes and dendritic cells, as well as antiretroviral activity have been reported, [8][9][10][11][12][13] a multitude of reports point to immune suppressive influences that may dominate IL-27 biology. Collectively, IL-27 has been shown to limit Th1, Th2 and Th17 responses while inducing T regulatory cells.…”