Department of Biology, Briar Cliff University, Sioux City, IA, USA.
Immunology. 2015 Apr;144(4):649-60. doi: 10.1111/imm.12417.
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.
树突状细胞(DCs)是一种强有力的抗原呈递细胞,对于建立有效的适应性免疫反应是必需的。在 DC 分化时存在的细胞因子环境可能是决定 DC 表型和功能特性的一个重要但经常被忽视的因素。白细胞介素-27(IL-27)是一种独特的细胞因子,具有炎症和免疫抑制活性。虽然它可以促进和抑制不同 T 细胞亚群的活性,但对巨噬细胞和 DC 的抗炎活性大多已被描述。然而,IL-27 在 DC 分化过程中的具体作用以及这种作用如何改变抗原呈递细胞的性质尚未得到研究。在本报告中,我们显示在单核细胞来源的 DC 分化过程中用 IL-27 处理可增强抗原加工和刺激 T 细胞活性的能力。在 IL-27 存在的情况下分化的 DC 显示出含乳胶珠的吞噬体酸化增强,这与液泡型 ATP 酶表达升高一致。这导致金黄色葡萄球菌的细胞内生长受到抑制。此外,在 IL-27 存在的情况下分化的 DC 表面 MHC Ⅱ类表达水平更高。在金黄色葡萄球菌感染时,IL-27 分化的 DC 中 IL-12 的产生也显著增加。这些活性的净效应是增强 CD4(+)T 细胞增殖和 T 辅助型 1 细胞因子的产生。这些发现对于广泛的免疫学背景非常重要,并且应该在未来疫苗的开发中加以考虑。