Inhibition of Immune Synapse by Altered Dendritic Cell Actin Distribution: A New Pathway of Mesenchymal Stem Cell Immune Regulation
Inhibition of Immune Synapse by Altered Dendritic Cell Actin Distribution: A New Pathway of Mesenchymal Stem Cell Immune Regulation
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DOI：
10.4049/jimmunol.1001332
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发表时间：
2010-11-01
影响因子：
4.4
通讯作者：
Ballerini, Clara
中科院分区：
文献类型：
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作者：
Aldinucci, Alessandra;Rizzetto, Lisa;Ballerini, Clara
树突状细胞 (DC) 和 T 细胞之间的免疫突触形成是免疫反应中的关键事件之一。在免疫原性突触中，完全成熟的 DC 的存在是强制性的；因此，调节 DC 成熟可能会促进耐受性，并代表了自身免疫性疾病的一种有价值的治疗方法。在细胞治疗领域，骨髓间充质干细胞（MSC）因其免疫调节特性而被广泛研究，例如在体外分化过程中抑制DC免疫原性和改善自身免疫性疾病（例如实验性过敏性脑脊髓炎）的体内模型。 MSC 似乎与 DC 发挥不同的作用，具体取决于细胞浓度、刺激机制和伴随的免疫细胞。这项工作的目的是阐明 DC 激活（LPS 刺激或 Ag 负载）过程中 MSC/DC 相互作用的免疫原性效应。本研究使用人类单核细胞来源的 DC、骨髓来源的 MSC 和从健康供体获得的循环淋巴细胞，以及实验室产生的流感病毒血凝素衍生肽、aa 306-318 肽特异性 T 细胞系。我们证明 MSC 仅在细胞与细胞接触时介导 DC 功能的抑制。尽管没有观察到细胞表型或细胞因子产生的改变，但经 MSC 处理的 DC 无法形成活跃的免疫突触；它们保留了未成熟 DC 的典型内吞活性和足小体样结构。 MSC-DC直接相互作用诱导的转录程序在分子途径水平上支持观察到的表型特征，表明参与接触诱导的DC细胞骨架重排的基因。免疫学杂志，2010，185：5102-5110。
Immune synapse formation between dendritic cells (DCs) and T cells is one of the key events in immune reaction. In immunogenic synapses, the presence of fully mature DCs is mandatory; consequently, the modulation of DC maturation may promote tolerance and represents a valuable therapeutic approach in autoimmune diseases. In the field of cell therapy, bone marrow mesenchymal stem cells (MSCs) have been extensively studied for their immunoregulatory properties, such as inhibiting DC immunogenicity during in vitro differentiation and ameliorating in vivo models of autoimmune diseases (e. g., experimental allergic encephalomyelitis). MSCs seem to play different roles with regard to DCs, depending on cell concentration, mechanism of stimulation, and accompanying immune cells. The aim of this work was to elucidate the immunogenic effects of MSC/DC interactions during DC activation (LPS stimulation or Ag loading). Human monocyte-derived DCs, bone marrow-derived MSCs, and circulating lymphocytes obtained from healthy donors, as well as the laboratory-generated influenza virus hemagglutinin-derived peptide, aa 306-318 peptide-specific T cell line were used for this study. We demonstrate that MSCs mediate inhibition of DC function only upon cell-cell contact. Despite no modification observed in cell phenotype or cytokine production, MSC-treated DCs were unable to form active immune synapses; they retained endocytic activity and podosome-like structures, typical of immature DCs. The transcriptional program induced by MSC-DC direct interaction supports at the molecular pathway level the phenotypical features observed, indicating the genes involved into contact-induced rearrangement of DC cytoskeleton. The Journal of Immunology, 2010, 185: 5102-5110.