Satoh Takashi
Department of Immunology, Graduate School and Faculty of Medicine, Tokyo Medical and Dental University (TMDU).
Nihon Yakurigaku Zasshi. 2023;158(4):298-303. doi: 10.1254/fpj.23007.
Macrophages have been discovered more than 100 years ago. Recent studies indicated that monocytes and macrophages can be categorized into several distinct phenotypes and their respective differentiation mechanisms are known. We also reported that the Jmjd3 is critical for the macrophage subtype activated by allergic stimuli and that the tissue resident macrophage subtype in adipose tissue, which is controlled by Trib1, is responsible for maintaining homeostasis of peripheral tissues such as adipocyte. Thus, it is considered that various macrophage/monocyte subtypes corresponding to certain disorders were existed in our body. Furthermore, in order to investigate the relationship between macrophage subtype and disease, we focused on fibrosis as the next target disease. Its pathogenesis is poorly understood, and there are few effective therapies. Previously we found that a new macrophage/monocyte subtype, which their markers are Msr1Ceacam1Ly6CMac1F4/80monocyte and share granulocyte characteristics, involved in development of fibrosis was accumulated in the affected area in the lungs at the beginning of fibrosis. We termed the monocyte/ macrophage subtype segregated-nucleus-containing atypical monocytes (SatM). Towards understanding the mechanism of fibrosis onset, we next focused on investigation of non-haematopoietic cells involved in activation of immune cell such as SatM during fibrotic phase.
巨噬细胞早在100多年前就已被发现。最近的研究表明,单核细胞和巨噬细胞可分为几种不同的表型,且它们各自的分化机制也已为人所知。我们还报道过,Jmjd3对于由过敏刺激激活的巨噬细胞亚型至关重要,而由Trib1控制的脂肪组织中的组织驻留巨噬细胞亚型负责维持诸如脂肪细胞等外周组织的稳态。因此,人们认为我们体内存在着与某些疾病相对应的各种巨噬细胞/单核细胞亚型。此外,为了研究巨噬细胞亚型与疾病之间的关系,我们将纤维化作为下一个目标疾病。其发病机制尚不清楚,且有效疗法很少。此前我们发现,一种新的巨噬细胞/单核细胞亚型,其标志物为Msr1、Ceacam1、Ly6C、Mac1、F4/80单核细胞并具有粒细胞特征,参与纤维化发展,在纤维化初期在肺部的病变区域积聚。我们将这种单核细胞/巨噬细胞亚型称为含分离核的非典型单核细胞(SatM)。为了了解纤维化发病的机制,接下来我们专注于研究在纤维化阶段参与激活免疫细胞(如SatM)的非造血细胞。