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

机译:白细胞介素27在单核细胞衍生的树突状细胞分化过程中的存在促进了抗原加工和对T细胞的刺激

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摘要

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.
机译:树突状细胞(DC)是建立有效的适应性免疫反应所必需的有效抗原呈递细胞。 DC分化时存在的细胞因子环境可能是一个重要的决定因素,但在DC的表型和功能特性方面常常被忽略。白介素27(IL-27)是一种独特的细胞因子,具有炎症和免疫抑制活性。尽管它可以促进和对抗不同T细胞亚群的活性,但大多数针对巨噬细胞和DC的抗炎活性已有描述。然而,尚未研究IL-27在DC分化期间的特异性作用以及其如何改变抗原呈递细胞的性质。在此报告中,我们表明在单核细胞衍生的DC分化过程中进行IL-27治疗可增强处理抗原和刺激T细胞活性的能力。在IL-27存在下分化的DC显示出增强的含乳胶珠吞噬体的酸化,这与液泡-ATPase的表达升高相一致。这导致抑制了金黄色葡萄球菌的细胞内生长。另外,在IL-27存在下分化的DC中,MHC II类表面表达水平更高。在金黄色葡萄球菌感染IL-27分化的DC期间,IL-12的产生也显着增加。这些活动的净效应是增强CD4(+)T细胞增殖和T辅助1型细胞因子的产生。这些发现对许多免疫学背景都很重要,应在未来疫苗的开发中加以考虑。

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