探討代謝基因在巨噬細胞分化所扮演的角色

Abstract

Macrophages are a type of immune cells that have the ability to engulf and digest foreign substances by phagocytosis, antigen presentation, anti-microbial activity and wound healing. Furthermore, macrophages play an important role in innate immunity and assist initiation of adaptive immunity by recruiting other immune cells such as dendritic cells and lymphocytes. There are two major subsets of macrophages, M1 and M2, which have distinct functions and features. Recent studies indicated that metabolism is important for regulating macrophage function and phenotype. However, whether the cellular metabolism in macrophage affects the differentiation of M1 and M2 remains unclear. Therefore, the aim of my research is to investigate the role of metabolic genes in macrophage differentiation. First, I performed macrophage development from bone marrow (BM) cells and immortalized bone marrow (imBM) cell line in vitro, and I showed BM cells and imBM cell line can develop into macrophages with L929 culture supernatant containing M-CSF. Next, I characterized the differentiation of macrophage from BM cells and imBM cell line in vitro. Bone marrow-derived macrophage (BMDM) and immortalized bone marrow cell line macrophage (imBMM) can differentiated into M1 and M2 subsets stimulated by LPS/IFN- and IL-4/IL-13, respectively. Further, we employed bioinformatics analysis assay to select the candidate metabolic genes expressed more than two-fold difference between M1/M2 in both human and mice. Next, I have confirmed these candidate genes expression in the subsets of macrophages derived from BMDMs and imBMMs. We knockdowned these candidate metabolic genes in imBMs by shRNA and identified some candidate metabolic genes could affect macrophage differentiation. We’ll confirm these results in BM cells in vitro.