Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Institute for Global Prominent Research, Chiba University, Chiba, Japan.
Immunol Rev. 2022 Jan;305(1):137-151. doi: 10.1111/imr.13056. Epub 2021 Dec 21.
Epigenetic regulation of gene transcription in the immune system is important for proper control of protective and pathogenic inflammation. Aberrant epigenetic modifications are often associated with dysregulation of the immune cells, including lymphocytes and macrophages, leading to pathogenic inflammation and autoimmune diseases. Two classical epigenetic markers-histone modifications and DNA cytosine methylation, the latter is the 5 position of the cytosine base in the context of CpG dinucleotides-play multiple roles in the immune system. CxxC domain-containing proteins, which basically bind to the non-methylated CpG (i.e., epigenetic "readers"), often function as "writers" of the epigenetic markers via their catalytic domain within the proteins or by interacting with other epigenetic modifiers. We herein report the most recent advances in our understanding of the functions of CxxC domain-containing proteins in the immune system and inflammation, mainly focusing on T cells and macrophages.
免疫系统中转录基因的表观遗传调控对于保护性和致病性炎症的适当控制非常重要。异常的表观遗传修饰通常与免疫细胞(包括淋巴细胞和巨噬细胞)的失调有关,导致致病性炎症和自身免疫性疾病。两种经典的表观遗传标记物——组蛋白修饰和 DNA 胞嘧啶甲基化,后者是指在 CpG 二核苷酸背景下胞嘧啶碱基的第 5 位——在免疫系统中发挥多种作用。CXXC 结构域蛋白主要与非甲基化的 CpG(即表观遗传“读取器”)结合,通常通过其蛋白内的催化结构域或与其他表观遗传修饰物相互作用,作为表观遗传标记物的“写入器”。本文主要介绍了我们对 CXXC 结构域蛋白在免疫系统和炎症中的功能的最新认识,主要集中在 T 细胞和巨噬细胞上。