Schmidleithner Lisa, Stüve Philipp, Feuerer Markus
Leibniz Institute for Immunotherapy, Regensburg, Germany.
Chair for Immunology, University Regensburg, Regensburg, Germany.
Nat Rev Immunol. 2025 Apr 29. doi: 10.1038/s41577-025-01172-3.
Transposable elements (TEs) are mobile repetitive nucleic acid sequences that have been incorporated into the genome through spontaneous integration, accounting for almost 50% of human DNA. Even though most TEs are no longer mobile today, studies have demonstrated that they have important roles in different biological processes, such as ageing, embryonic development, and cancer. TEs influence these processes through various mechanisms, including active transposition of TEs contributing to ongoing evolution, transposon transcription generating RNA or protein, and by influencing gene regulation as enhancers. However, how TEs interact with the immune system remains a largely unexplored field. In this Perspective, we describe how TEs might influence different aspects of the immune system, such as innate immune responses, T cell activation and differentiation, and tissue adaptation. Furthermore, TEs can serve as a source of neoantigens for T cells in antitumour immunity. We suggest that TE biology is an important emerging field of immunology and discuss the potential to harness the TE network therapeutically, for example, to improve immunotherapies for cancer and autoimmune and inflammatory diseases.
转座元件（TEs）是可移动的重复核酸序列，通过自发整合已融入基因组，占人类DNA的近50%。尽管如今大多数转座元件已不再具有移动性，但研究表明它们在不同的生物学过程中发挥着重要作用，如衰老、胚胎发育和癌症。转座元件通过多种机制影响这些过程，包括参与持续进化的转座元件的活跃转座、转座子转录产生RNA或蛋白质，以及作为增强子影响基因调控。然而，转座元件如何与免疫系统相互作用在很大程度上仍是一个未被探索的领域。在这篇观点文章中，我们描述了转座元件可能如何影响免疫系统的不同方面，如先天免疫反应、T细胞活化和分化以及组织适应性。此外，转座元件可作为抗肿瘤免疫中T细胞新抗原的来源。我们认为转座元件生物学是一个重要的新兴免疫领域，并讨论了利用转座元件网络进行治疗的潜力，例如改善癌症、自身免疫性疾病和炎症性疾病的免疫疗法。
