Jay Atishay, Pondevida Carlos M, Vahedi Golnaz
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nat Immunol. 2025 Apr;26(4):544-556. doi: 10.1038/s41590-025-02113-x. Epub 2025 Mar 19.
Specialized T cell subsets mediate adaptive immunity in response to cytokine signaling and specific transcription factor activity. The epigenetic landscape of T cells has an important role in facilitating and establishing T cell fate decisions. Here, we review the interplay between transcription factors, histone modifications, DNA methylation and three-dimensional chromatin organization to define key elements of the epigenetic landscape in T cells. We introduce key technologies in the areas of sequencing, microscopy and proteomics that have enabled the multi-scale profiling of the epigenetic landscape. We highlight the dramatic changes of the epigenetic landscape as multipotent progenitor cells commit to the T cell lineage during development and discuss the epigenetic changes that favor the emergence of CD4 and CD8 T cells. Finally, we discuss the inheritance of epigenetic marks and its potential effects on immune responses as well as therapeutic strategies with potential for epigenetic regulation.
特化的T细胞亚群通过细胞因子信号传导和特定转录因子活性介导适应性免疫。T细胞的表观遗传格局在促进和确立T细胞命运决定中发挥重要作用。在此，我们综述转录因子、组蛋白修饰、DNA甲基化和三维染色质组织之间的相互作用，以界定T细胞表观遗传格局的关键要素。我们介绍测序、显微镜和蛋白质组学领域的关键技术，这些技术实现了对表观遗传格局的多尺度分析。我们强调在发育过程中多能祖细胞分化为T细胞谱系时表观遗传格局的显著变化，并讨论有利于CD4和CD8 T细胞出现的表观遗传变化。最后，我们讨论表观遗传标记的遗传及其对免疫反应的潜在影响，以及具有表观遗传调控潜力的治疗策略。
