生物谷报道：美国Pennsylvania大学医学院科学家最近发现免疫细胞自我“决定”变得活跃或不活跃的机制，这有助于癌症，自身免疫疾病和器官移植排异的治疗。病理和药学教授Gary A. Koretzky在最新的一期《Nature Immunology》上描述了T细胞是怎样不对目标细胞或蛋白质发生反应的。他们发现，一种叫做甘油二酯（DAGs）的脂肪酸以及一种酶是这一过程的关键因素。
免疫T淋巴细胞能识别身体的入侵者，如病毒，细菌，癌细胞或过敏原。正常情况下，T细胞会由一系列复杂信号激发，最后破坏外来物。但是有些T细胞处于未激发状态，这一过程保护免疫细胞自身和其它正常细胞不受攻击。 Koretzky表示：“T淋巴细胞怎样被激发是免疫学的主要问题之一。我们的研究发现DAGs是这些细胞对入侵者反应的关键。但是当DAGs被甘油二酯酶（DGKs）作用后，T细胞不再对目标作出反应。” 这一结果是通过研究去除了DGKs的小鼠后得出的。虽然这些小鼠的T细胞在大部分时候很正常，但DAGs无法得到DGKs的作用，所以T细胞会对外来抗原过度反应。 一种本不该引发免疫反应的葡萄球菌毒素使小鼠T细胞发生了过度反应。这证明是DGK的缺乏造成的。而且T细胞制造了多于正常五倍的免疫因子。
?过度反应如果能被控制，就能对身体有好处，例如T细胞能消灭癌细胞。研究者正在继续研究这些小鼠，看看它们是否能将癌细胞识别为入侵者并消灭它们。
Figure 1. Modeling of the molecular interactions between ITAM-containing and integrin receptors.
(a) ITAM receptor activation of integrins. 'Inside-out' activation signals necessary for integrin ligand binding can be generated via signaling by ITAMs through the protein tyrosine kinase Syk, the two adaptor proteins SLP-76 and Gads, and the phospholipase PLC- 2 in lipid rafts. (b) Pre-existing model of ITAM-independent integrin signaling through Syk, SLP-76 and PLC- 2. Prior studies using heterologous expression of signaling proteins in cell lines have suggested that after ligand binding, integrin -subunits might directly bind and activate Syk. (c) New model of ITAM-dependent, raft-independent integrin signaling through Syk, SLP-76 and PLC- 2. Genetic studies and in vivo structure-function analyses using primary cells now suggest that after ligand binding, integrins activate signaling through Syk, SLP-76 and PLC- 2 through engagement of ITAM-containing receptors by a mechanism that does not require recruitment to lipid rafts. Bent green lines (b,c) indicate the active integrin conformation. How integrins engage ITAM-containing receptors is not known, but it may be through adhesion of both receptors to a common ligand or via more direct receptor interaction.
原文出处：
Nat Immunol. 2006 Dec;7(12):1286-8
Integrins and ITAMs: more than just good neighbors.
Kahn ML, Koretzky GA.
