Emerging insights and challenges for understanding T cell function through the proteome.
Emerging insights and challenges for understanding T cell function through the proteome.
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DOI：
10.3389/fimmu.2022.1028366
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发表时间：
2022
影响因子：
7.3
通讯作者：
Solt, Laura A.
中科院分区：
文献类型：
--
作者：
Solt, Laura A.
T细胞在暴露于同源抗原时从静止状态快速转变为活跃的增殖和效应子功能。这些过程受到信号转导途径的严格控制，这些途径影响染色质重塑、基因转录和代谢的变化，所有这些共同驱动特定的T细胞记忆或效应细胞发育。任何这些事件的失调都可以介导疾病，过去几年已经显示出前所未有的新方法来理解这些事件，直到单细胞水平。在单细胞水平上评估基因组和转录组的测序方法的大规模爆炸改变了我们对正常和各种疾病状态下T细胞活化，发育潜力和效应功能的理解。尽管取得了这些进展，但关于这些事件如何转化为蛋白质水平的信息仍然非常缺乏。例如，介导T细胞功能的蛋白质同种型和/或特异性翻译后修饰的解析仍然不清楚。蛋白质组学的应用可以改变这一点，使人们能够深入了解调节T细胞功能的分子机制。然而，与在mRNA和染色质水平上实现T细胞动力学的精细可视化的基因组方法不同，蛋白质组学方法，包括单细胞水平上的方法，已经显着落后。在这篇综述中，我们描述了最近的研究，使人们能够更好地了解蛋白质的合成和降解过程中的T细胞活化和收购效应功能的变化。我们还强调了技术进步以及如何将其应用于T细胞生物学。最后，我们讨论了未来需要扩大我们目前的知识T细胞蛋白质组和疾病。
T cells rapidly transition from a quiescent state into active proliferation and effector function upon exposure to cognate antigen. These processes are tightly controlled by signal transduction pathways that influence changes in chromatin remodeling, gene transcription, and metabolism, all of which collectively drive specific T cell memory or effector cell development. Dysregulation of any of these events can mediate disease and the past several years has shown unprecedented novel approaches to understand these events, down to the single-cell level. The massive explosion of sequencing approaches to assess the genome and transcriptome at the single cell level has transformed our understanding of T cell activation, developmental potential, and effector function under normal and various disease states. Despite these advances, there remains a significant dearth of information regarding how these events are translated to the protein level. For example, resolution of protein isoforms and/or specific post-translational modifications mediating T cell function remains obscure. The application of proteomics can change that, enabling significant insights into molecular mechanisms that regulate T cell function. However, unlike genomic approaches that have enabled exquisite visualization of T cell dynamics at the mRNA and chromatin level, proteomic approaches, including those at the single-cell level, has significantly lagged. In this review, we describe recent studies that have enabled a better understanding of how protein synthesis and degradation change during T cell activation and acquisition of effector function. We also highlight technical advances and how these could be applied to T cell biology. Finally, we discuss future needs to expand upon our current knowledge of T cell proteomes and disease.
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