Adoue Véronique, Joffre Olivier
Centre de Physiopathologie Toulouse Purpan, Inserm U1043 - BP 3028, 31024 Toulouse Cedex 3, France.
Med Sci (Paris). 2020 Mar;36(3):253-260. doi: 10.1051/medsci/2020022. Epub 2020 Mar 31.
Upon priming by dendritic cells, naïve CD4 T lymphocytes are exposed to distinct molecular environments depending on the nature of the pathological stimulus. In response, they mobilize different gene networks that establish lineage-specific developmental programs, and coordinate the acquisition of specific phenotype and functions. Accordingly, CD4 T cells are capable of differentiation into a large variety of functionally-distinct T helper (Th) cell subsets. In this review, we describe the molecular events that control CD4 T cell differentiation at the level of the chromatin. We insist on recent works that have highlighted the key role of H3K9me3-dependent epigenetic mechanisms in the regulation of T cell identity. Interestingly, these pathways shape and control the developmental programs at least in part through the regulation of endogenous retroviruses-derived sequences that have been exapted into cis-regulatory modules of Th genes.
在树突状细胞启动后,初始CD4 T淋巴细胞会根据病理刺激的性质暴露于不同的分子环境中。作为响应,它们调动不同的基因网络,这些网络建立谱系特异性的发育程序,并协调特定表型和功能的获得。因此,CD4 T细胞能够分化为多种功能不同的辅助性T(Th)细胞亚群。在本综述中,我们描述了在染色质水平上控制CD4 T细胞分化的分子事件。我们着重介绍了最近的研究工作,这些工作突出了H3K9me3依赖性表观遗传机制在T细胞身份调节中的关键作用。有趣的是,这些途径至少部分地通过调节已被纳入Th基因顺式调节模块的内源性逆转录病毒衍生序列来塑造和控制发育程序。