Disorder specific macrophage subtype -Towards understanding the mechanism of fibrosis onset-

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 (Nat. Immunol. 2010) 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 (Nature. 2013). 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 monocyte 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) (Nature. 2017). 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.