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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Beyond DNA repair, the immunological role of PARP-1 and its siblings
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Beyond DNA repair, the immunological role of PARP-1 and its siblings

机译：除DNA修复外，PARP-1及其兄弟姐妹的免疫功能

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ADP-ribosylation is the addition of one or more (up to some hundreds) ADP-ribose moieties to acceptor proteins. There are two major families of enzymes that catalyse this reaction: extracellular ADP-ribosyl-transferases (ARTs), which are bound to the cell membrane by a glycosylphosphatidylinositol anchor or are secreted, and poly(ADP-ribose)-polymerases (PARPs), which are present in the cell nucleus and/or cytoplasm. Recent findings revealed a wide immunological role for ADP-ribosylating enzymes. ARTs, by sensing extracellular NAD concentration, can act as danger detectors. PARP-1, the prototypical representative of the PARP family, known to protect cells from genomic instability, is involved in the development of inflammatory responses and several forms of cell death. PARP-1 also plays a role in adaptive immunity by modulating the ability of dendritic cells to stimulate T cells or by directly affecting the differentiation and functions of T and B cells. Both PARP-1 and PARP-14 (CoaSt6) knockout mice were described to display reduced T helper type 2 cell differentiation and allergic responses. Our recent findings showed that PARP-1 is involved in the differentiation of Foxp3+ regulatory T (Treg) cells, suggesting a role for PARP-1 in tolerance induction. Also ARTs regulate Treg cell homeostasis by promoting Treg cell apoptosis during inflammatory responses. PARP inhibitors ameliorate immune-mediated diseases in several experimental models, including rheumatoid arthritis, colitis, experimental autoimmune encephalomyelitis and allergy. Together these findings show that ADP-ribosylating enzymes, in particular PARP-1, play a pivotal role in the regulation of immune responses and may represent a good target for new therapeutic approaches in immune-mediated diseases.
机译：ADP-核糖基化是向受体蛋白中添加一个或多个（多达数百个）ADP-核糖部分。催化该反应的酶主要有两个家族：胞外ADP-核糖基转移酶（ARTs）（通过糖基磷脂酰肌醇锚固或分泌到细胞膜上）和聚（ADP-核糖）聚合酶（PARP）存在于细胞核和/或细胞质中。最近的发现揭示了ADP-核糖基化酶的广泛免疫学作用。通过感应细胞外NAD浓度，ART可以充当危险检测器。 PARP-1是PARP家族的典型代表，已知可以保护细胞免受基因组不稳定的影响，它参与了炎症反应的发展和多种细胞死亡形式。 PARP-1还通过调节树突状细胞刺激T细胞的能力或直接影响T细胞和B细胞的分化和功能，在适应性免疫中发挥作用。 PARP-1和PARP-14（CoaSt6）基因敲除小鼠均表现出2型T辅助细胞分化和过敏反应减少。我们最近的发现表明，PARP-1与Foxp3 +调节性T细胞（Treg）的分化有关，提示PARP-1在耐受诱导中的作用。 ARTs还通过在炎症反应过程中促进Treg细胞凋亡来调节Treg细胞的稳态。 PARP抑制剂可在多种实验模型中改善免疫介导的疾病，包括类风湿性关节炎，结肠炎，实验性自身免疫性脑脊髓炎和过敏。这些发现共同表明，ADP-核糖基化酶，特别是PARP-1，在调节免疫应答中起关键作用，并且可能代表免疫介导疾病中新治疗方法的良好靶标。

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