Kempkes Rosalie W M, Prinjha Rab K, de Winther Menno P J, Neele Annette E
Amsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Disease, Amsterdam, the Netherlands.
Science@RabP Ltd.
Trends Immunol. 2024 Dec;45(12):1015-1030. doi: 10.1016/j.it.2024.10.003. Epub 2024 Nov 27.
The polycomb repressive complex 2 (PRC2) is an established therapeutic target in cancer. PRC2 catalyzes methylation of histone H3 at lysine 27 (H3K27me3) and is known for maintaining eukaryote cell identity. Recent discoveries show that modulation of PRC2 not only impacts cell differentiation and tumor growth but also has immunomodulatory properties. Here, we integrate multiple immunological fields to understand PRC2 and its subunits in epigenetic canonical regulation and non-canonical mechanisms within innate immunity. We discuss how PRC2 regulates hematopoietic stem cell proliferation, myeloid cell differentiation, and shapes innate immune responses. The PRC2 catalytic domain EZH2 is upregulated in various human inflammatory diseases and its deletion or inhibition in experimental mouse models can reduce disease severity, emphasizing its importance in regulating inflammation.
多梳抑制复合物2（PRC2）是一种已确定的癌症治疗靶点。PRC2催化组蛋白H3赖氨酸27位点的甲基化（H3K27me3），并以维持真核细胞特性而闻名。最近的发现表明，对PRC2的调控不仅会影响细胞分化和肿瘤生长，还具有免疫调节特性。在此，我们整合多个免疫学领域，以了解PRC2及其亚基在表观遗传经典调控以及固有免疫中的非经典机制。我们讨论了PRC2如何调节造血干细胞增殖、髓样细胞分化以及塑造固有免疫反应。PRC2催化结构域EZH2在多种人类炎症性疾病中上调，在实验小鼠模型中对其进行缺失或抑制可降低疾病严重程度，这凸显了其在调节炎症中的重要性。
