Novel role for galectin-1 in T-cells under physiological and pathological conditions
Novel role for galectin-1 in T-cells under physiological and pathological conditions
复制标题
DOI：
10.1016/j.imbio.2014.10.023
复制
发表时间：
2015-04-01
期刊：
影响因子：
2.8
通讯作者：
Kovacs, Laszlo
中科院分区：
文献类型：
--
作者：
Deak, Magdolna;Hornung, Akos;Kovacs, Laszlo
分泌的胞外半乳糖凝集素-1（exGal-1）而非胞内Gal-1（inGal-1）由于其诱导活化T细胞凋亡的主要活性而被描述为强免疫抑制蛋白。先前已经报道，T细胞在活化时表达Gal-1，然而其参与T细胞功能在很大程度上仍然是难以捉摸的。为了确定由活化的T细胞表达的Gal-1的功能，我们进行了一系列实验。我们已经表明，在Gal-1转基因Jurkat细胞或活化的T细胞中表达的Gal-1保持在细胞内，表明Gal-1诱导的T细胞死亡不是从头表达的Gal-1的自分泌效应的结果。相反，inGal-1表达的一个特殊结果是T细胞对作为可溶性蛋白或结合到分泌Gal-1的效应细胞表面的exGal-1变得更敏感。当比较来自野生型或Gal-1敲除小鼠的活化T细胞对Gal-1诱导的细胞凋亡的易感性时，也证实了这一点。表达Gal-1的小鼠T细胞对exGal-1的细胞毒性比其Gal-1敲除对应物更敏感。我们还对系统性红斑狼疮（SLE）患者的活化T细胞进行了研究，SLE是一种T细胞凋亡失调的疾病。SLE T细胞比健康T细胞表达更低量的Gal-1，并且对exGal-1不太敏感。这些结果表明，一个新的作用inGal-1在T细胞作为一个调节器的T细胞反应exGal-1，其可能的贡献机制，在T细胞凋亡缺陷狼疮。(C)2014 Elsevier GmbH. All rights reserved.
Secreted, extracellular galectin-1 (exGal-1) but not intracellular Gal-1 (inGal-1) has been described as a strong immunosuppressive protein due to its major activity of inducing apoptosis of activated T-cells. It has previously been reported that T-cells express Gal-1 upon activation, however its participation in T-cell functions has remained largely elusive. To determine function of Gal-1 expressed by activated T-cells we have carried out a series of experiments. We have shown that Gal-1, expressed in Gal-1-transgenic Jurkat cells or in activated T-cells, remained intracellularly indicating that Gal-1-induced T-cell death was not a result of an autocrine effect of the de novo expressed Gal-1. Rather, a particular consequence of the inGal-1 expression was that T-cells became more sensitive to exGal-1 added either as a soluble protein or bound to the surface of a Gal-1-secreting effector cell. This was also verified when the susceptibility of activated T-cells from wild type or Gal-1 knockout mice to Gal-1-induced apoptosis were compared. Murine T-cells expressing Gal-1 were more sensitive to the cytotoxicity of the exGal-1 than their Gal-1 knockout counterparts. We also conducted a study with activated T-cells from patients with systemic lupus erythematosus (SLE), a disease in which dysregulated T-cell apoptosis has been well described. SLE T-cells expressed lower amounts of Gal-1 than healthy T-cells and were less sensitive to exGal-1. These results suggested a novel role of inGal-1 in T-cells as a regulator of T-cell response to exGal-1, and its likely contribution to the mechanism in T-cell apoptosis deficiency in lupus. (C) 2014 Elsevier GmbH. All rights reserved.