Quantitative Proteomics Reveals GIMAP Family Proteins 1 and 4 to Be Differentially Regulated during Human T Helper Cell Differentiation
Quantitative Proteomics Reveals GIMAP Family Proteins 1 and 4 to Be Differentially Regulated during Human T Helper Cell Differentiation
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DOI：
10.1074/mcp.m800139-mcp200
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发表时间：
2009-01-01
影响因子：
7
通讯作者：
Lahesmaa, Riitta
中科院分区：
文献类型：
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作者：
Filen, Jan-Jonas;Filen, Sanna;Lahesmaa, Riitta
T 辅助 (Th) 细胞分化为功能不同的效应细胞亚群，其中 Th1 和 Th2 细胞的特征最为明显。除了 T 细胞受体信号传导之外，IL-12 诱导的 STAT4 以及 T-bet 和 IL-4 诱导的 STAT6 和 GATA3 信号传导途径分别是调节 Th1 和 Th2 分化过程的主要参与者。然而，可能还涉及其他未知因素或途径。在这项研究中，我们利用定量蛋白质组学，利用可裂解的 ICAT 标记和 LC-MS/MS 来鉴定从脐带血中提取的 CD4+ 细胞微粒体部分中的 IL-4 调节蛋白。我们能够鉴定出 557 种蛋白质，其中 304 种还被定量。本研究确定了 Th2 分化过程中 IL-4 对小 GTP 酶 GIMAP1 和 GIMAP4 的下调。我们还发现，在诱导分化为 Th1 谱系的细胞中，GIMAP1 和 GIMAP4 基因均被 IL-12 和其他 Th1 分化诱导细胞因子上调，而在诱导分化为 Th2 的细胞中，GIMAP1 和 GIMAP4 基因被 IL-4 下调。我们的结果表明，GIMAP（免疫相关蛋白的 GTP 酶）蛋白家族在 Th 细胞分化过程中受到差异性调节。分子与细胞蛋白质组学 8:32-44, 2009。
T helper (Th) cells differentiate into functionally distinct effector cell subsets of which Th1 and Th2 cells are best characterized. Besides T cell receptor signaling, IL-12-induced STAT4 and T-bet- and IL-4-induced STAT6 and GATA3 signaling pathways are the major players regulating the Th1 and Th2 differentiation process, respectively. However, there are likely to be other yet unknown factors or pathways involved. In this study we used quantitative proteomics exploiting cleavable ICAT labeling and LC-MS/MS to identify IL-4-regulated proteins from the microsomal fractions of CD4(+) cells extracted from umbilical cord blood. We were able to identify 557 proteins of which 304 were also quantified. This study resulted in the identification of the down-regulation of small GTPases GIMAP1 and GIMAP4 by IL-4 during Th2 differentiation. We also showed that both GIMAP1 and GIMAP4 genes are up-regulated by IL-12 and other Th1 differentiation-inducing cytokines in cells induced to differentiate toward Th1 lineage and down-regulated by IL-4 in cells induced to Th2. Our results indicate that the GIMAP (GTPase of the immunity-associated protein) family of proteins is differentially regulated during Th cell differentiation. Molecular & Cellular Proteomics 8:32-44, 2009.