Functional diversity of disorder-specific macrophages

Abstract

Recent research has revealed that macrophages and monocytes comprise various subtypes. Previously, we demonstrated that JMJD3 is vital for macrophage differentiation in response to allergic stimuli. Moreover, we substantiated that Trib1 controls the differentiation of tissue-resident macrophages in peripheral organs, such as adipose tissue. This study aims to elucidate that Ceacam1⁺Msr1⁺Ly6C⁻F4/80⁻Mac1⁺ monocytes are essential for the development of fibrosis. Remarkably, these cell types harbor bilobed-like nucleus and some granules in the cytoplasm. Thus, we named these as cell segregated-nucleus-containing atypical monocytes (SatM). The results revealed that NFIL6 is critical for the differentiation of SatM, and the lack of this protein causes a complete deficiency of SatM. Furthermore, the development of fibrosis was prevented in NFIL6^−/− chimeric mice and the adoptive transfer of SatM into NFIL6^−/− chimeric mice resulted in fibrosis. Thus, macrophage and monocytes comprised multiple subtypes with functional diversity.