Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Center for Cancer Cell Biology, Immunology, and Infection, Discipline of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, IL.
J Immunol. 2023 Sep 1;211(5):721-726. doi: 10.4049/jimmunol.2200757.
CTL differentiation is controlled by the crosstalk of various transcription factors and epigenetic modulators. Uncovering this process is fundamental to improving immunotherapy and designing novel therapeutic approaches. In this study, we show that polycomb repressive complex 1 subunit chromobox (Cbx)4 favors effector CTL differentiation in a murine model. Cbx4 deficiency in CTLs induced a transcriptional signature of memory cells and increased the memory CTL population during acute viral infection. It has previously been shown that besides binding to H3K27me3 through its chromodomain, Cbx4 functions as a small ubiquitin-like modifier (SUMO) E3 ligase in a SUMO-interacting motifs (SIM)-dependent way. Overexpression of Cbx4 mutants in distinct domains showed that this protein regulates CTL differentiation primarily in an SIM-dependent way and partially through its chromodomain. Our data suggest a novel role of a polycomb group protein Cbx4 controlling CTL differentiation and indicated SUMOylation as a key molecular mechanism connected to chromatin modification in this process.
CTL 分化受各种转录因子和表观遗传调节剂的相互作用控制。揭示这一过程对于改善免疫疗法和设计新的治疗方法至关重要。在这项研究中，我们表明多梳抑制复合物 1 亚基 chromobox (Cbx)4 有利于在小鼠模型中效应 CTL 的分化。CTL 中 Cbx4 的缺失诱导了记忆细胞的转录特征，并在急性病毒感染期间增加了记忆 CTL 群体。先前已经表明，除了通过其 chromodomain 与 H3K27me3 结合外，Cbx4 还以依赖 SUMO 相互作用基序 (SIM) 的方式作为小泛素样修饰物 (SUMO) E3 连接酶发挥作用。在不同结构域中过表达 Cbx4 突变体表明，该蛋白主要通过 SIM 依赖性方式，部分通过其 chromodomain 调节 CTL 分化。我们的数据表明多梳蛋白 Cbx4 在控制 CTL 分化方面具有新的作用，并表明 SUMO 化作为与该过程中染色质修饰相关的关键分子机制。
