Dendritic cells (DCs) and macrophages are at the forefront of immune responses, modifying their transcriptional programs in response to their tissue environment or immunological challenge. Posttranslational modifications of histones, such as histone H3 lysine-27 trimethylation (H3K27me3) by the Polycomb repressive complex 2 (PRC2), are tightly associated with epigenetic regulation of gene expression. To explore whether H3K27me3 is involved in either the establishment or function of the mononuclear phagocyte system, we selectively deleted core components of PRC2, either EZH2 or SUZ12, in CD11c-expressing myeloid cells. Unexpectedly, EZH2 deficiency neither prevented the deposition and maintenance of H3K27me3 in DCs nor hindered DC/macrophage homeostasis. In contrast, SUZ12 deficiency markedly impaired the capacity of DCs and macrophages to maintain H3K27me3. SUZ12 ablation induced a rapid loss of the alveolar macrophage and Langerhans cell networks under both steady state and inflammatory conditions because these cells could no longer proliferate to facilitate their self-renewal. Despite the reduced H3K27me3, DC development and function were unaffected by SUZ12 ablation, suggesting that PRC2-mediated gene repression was dispensable for DC homeostasis. Thus, the role of SUZ12 highlights the fundamentally different homeostatic mechanisms used by tissue-resident myeloid cells versus DCs.

中文翻译：

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在树突状细胞和组织驻留骨髓细胞稳态中对 Polycomb 阻遏复合物 2 的差异要求

树突状细胞 (DC) 和巨噬细胞处于免疫反应的最前沿，它们会根据其组织环境或免疫学挑战修改其转录程序。组蛋白的翻译后修饰，例如 Polycomb 抑制复合物 2 (PRC2) 的组蛋白 H3 赖氨酸 27 三甲基化 (H3K27me3)，与基因表达的表观遗传调控密切相关。为了探索 H3K27me3 是否参与单核吞噬细胞系统的建立或功能，我们在表达 CD11c 的骨髓细胞中选择性地删除了 PRC2 的核心成分 EZH2 或 SUZ12。出乎意料的是，EZH2 缺乏既不会阻止 DCs 中 H3K27me3 的沉积和维持，也不会阻碍 DC/巨噬细胞稳态。相比之下，SUZ12 缺乏显着损害了 DCs 和巨噬细胞维持 H3K27me3 的能力。SUZ12 消融导致肺泡巨噬细胞和朗格汉斯细胞网络在稳态和炎症条件下迅速丧失，因为这些细胞不再能够增殖以促进其自我更新。尽管 H3K27me3 减少，但 DC 发育和功能不受 SUZ12 消融的影响，这表明 PRC2 介导的基因抑制对于 DC 稳态是可有可无的。因此，SUZ12 的作用突出了组织驻留骨髓细胞与 DC 使用的根本不同的稳态机制。SUZ12 消融导致肺泡巨噬细胞和朗格汉斯细胞网络在稳态和炎症条件下迅速丧失，因为这些细胞不再能够增殖以促进其自我更新。尽管 H3K27me3 减少，但 DC 发育和功能不受 SUZ12 消融的影响，这表明 PRC2 介导的基因抑制对于 DC 稳态是可有可无的。因此，SUZ12 的作用突出了组织驻留骨髓细胞与 DC 使用的根本不同的稳态机制。SUZ12 消融导致肺泡巨噬细胞和朗格汉斯细胞网络在稳态和炎症条件下迅速丧失，因为这些细胞不再能够增殖以促进其自我更新。尽管 H3K27me3 减少，但 DC 发育和功能不受 SUZ12 消融的影响，这表明 PRC2 介导的基因抑制对于 DC 稳态是可有可无的。因此，SUZ12 的作用突出了组织驻留骨髓细胞与 DC 使用的根本不同的稳态机制。