Interferon-α Abrogates the Suppressive Effect of Apoptotic Cells on Dendritic Cells in an In Vitro Model of Systemic Lupus Erythematosus Pathogenesis
Interferon-α Abrogates the Suppressive Effect of Apoptotic Cells on Dendritic Cells in an In Vitro Model of Systemic Lupus Erythematosus Pathogenesis
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DOI：
10.3899/jrheum.121299
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发表时间：
2013-10-01
影响因子：
3.9
通讯作者：
Kuhn, Annegret
中科院分区：
文献类型：
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作者：
Abeler-Doerner, Lucie;Rieger, Cosima C.;Kuhn, Annegret
目标。系统性红斑狼疮(SLE)的发病机制可能与细胞凋亡率增加和树突状细胞(DC)活化有关。我们研究了SLE患者中性粒细胞和单核细胞来源的树突状细胞的特征，它们之间的相互作用，以及自身抗体和炎性细胞因子对这种相互作用的影响。用流式细胞仪检测中性粒细胞凋亡和DC活化的动力学。为了分析凋亡细胞与吞噬细胞的相互作用，将SLE患者DC与凋亡的Jurkat T细胞以及SLE患者的凋亡中性粒细胞与单核细胞系U937进行交叉共培养实验。在此共培养体系中加入SLE血清和细胞因子，并通过炎症细胞因子分泌水平来量化DC的激活和抑制。与健康对照组相比，SLE患者的凋亡中性粒细胞和DC没有表现出固有的缺陷，它们相互作用的抑制性质也没有受到影响。自身抗体以及炎性细胞因子白介素17(IL-17)和白介素1β(IL-1β)对这种相互作用没有影响。然而，干扰素-α显著降低了凋亡细胞对DC的抑制作用。这些数据表明，SLE的异常免疫反应性通常不是由于凋亡细胞的内在缺陷，它们的处理或它们与DC的相互作用，而可能是这种相互作用发生的环境造成的。我们的研究强调了干扰素-α在系统性红斑狼疮早期阶段的重要性及其作为治疗靶点的潜力。
Objective. An increased incidence of apoptotic cells and an increased activation of dendritic cells (DC) may be involved in the pathogenesis of systemic lupus erythematosus (SLE). We investigated the characteristics of apoptotic neutrophils and monocyte-derived DC of patients with SLE, their interaction, and the influence of autoantibodies and inflammatory cytokines on this interaction.Methods. Kinetics of neutrophil apoptosis and DC activation were studied by flow cytometry. To analyze the interaction of apoptotic cells with phagocytes, crossover coculture experiments were performed with DC from patients with SLE and apoptotic Jurkat T cells as well as with apoptotic neutrophils from patients with SLE and the monocytic cell line U937. SLE serum and cytokines were added to this coculture, and activation and suppression of DC were quantified by levels of inflammatory cytokine secretion.Results. Apoptotic neutrophils and DC from patients with SLE showed no inherent defects compared to healthy controls, and the suppressive nature of their interaction was not affected. Autoantibodies as well as the inflammatory cytokines interleukin 17 (IL-17) and IL-1 beta had no influence on the interaction in this setup. Interferon (IFN)-alpha, however, substantially reduced the suppressive effect of apoptotic cells on DC.Conclusion. The data suggest that aberrant immune reactivity in SLE is not generally due to an intrinsic defect in apoptotic cells, their processing, or their interaction with DC, but likely arises from the milieu in which this interaction takes place. Our study highlights the importance of IFN-alpha during early stages of SLE and its potential as a therapeutic target.