Diacylglycerol kinases in immune cell function and self-tolerance.
Diacylglycerol kinases in immune cell function and self-tolerance.
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DOI：
10.1111/j.1600-065x.2008.00647.x
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发表时间：
2008-08
影响因子：
8.7
通讯作者：
Wan CK
中科院分区：
文献类型：
--
作者：
Zhong XP;Guo R;Zhou H;Liu C;Wan CK
甘油二酯(DAG)和磷脂酸(PA)都是重要的第二信使，参与多种免疫细胞受体的信号转导，可通过多种机制产生和代谢。最近的研究表明，催化DAG磷酸化以产生PA的二酰基甘油激酶(DGKs)在调节多种免疫细胞系的功能中发挥着关键作用。在T细胞中，两种DGK亚型，α和ζ，在T细胞受体结合后抑制DAG介导的信号转导，防止T细胞过度激活。DGK、α和ζ协同促进T细胞无能，对T细胞耐受性至关重要。在肥大细胞中，DGKζ通过促进脱颗粒和抑制高亲和力Ig E受体激活后细胞因子的产生，在肥大细胞的激活中发挥不同的作用。在树突状细胞和巨噬细胞中，DGKζ通过其产物PA正向调节Toll样受体诱导的促炎细胞因子的产生，对宿主抵御弓形虫感染起关键作用。这些研究表明，DGKs作为信号终止者和启动者，在调节免疫细胞功能中起着关键作用。
Both diacylglycerol (DAG) and phosphatidic acid (PA) are important second messengers involved in signal transduction from many immune cell receptors and can be generated and metabolized through multiple mechanisms. Recent studies indicate that diacylglycerol kinases (DGKs), the enzymes that catalyze phosphorylation of DAG to produce PA, play critical roles in regulating the functions of multiple immune cell lineages. In T cells, two DGK isoforms, α and ζ, inhibit DAG-mediated signaling following T cell receptor engagement and prevent T cell hyperactivation. DGKα and ζ synergistically promote T cell anergy and are critical for T cell tolerence. In mast cells, DGKζ plays differential roles in their activation by promoting degranulation but attenuating cytokine production following enagement of the high affinity receptor for IgE. In dendritic cells and macrophages, DGKζ positively regulates Toll-like receptor-induced proinflammatory cytokine production through its product PA, and is critical for host defense against Toxoplama gondii infection. These studies demonstrate pivotal roles of DGKs in regulating immune cell function by acting both as signal terminator and initiator.