Glycolysis regulates macrophage differentiation into IL-10 producing phenotype (INM6P.342)

There are a lot of reports indicating that cellular metabolic state or some metabolites regulate the phenotype of immune cells. In case of macrophages (Mϕ), it is believed that regulatory and inflammatory Mϕ shifts ATP production to each oxidative phosphorylation and glycolysis, respectively. However, it is not clear how metabolic pathway affects Mϕ in the acquisition of their specific phenotypes. In this report, we tried to reveal how glycolysis affects Mϕ during the acquisition of IL-10 producing phenotype. We used in vitro differentiated human monocyte derived Mϕ cultured in the presence of M-CSF or M-CSF plus IFNγ as IL-10 producing-Mϕ (M-Mϕ) or inflammatory Mϕ (Mγ-Mϕ), respectively. M-Mϕ showed regulatory Mϕ-like phenotypes and produced more IL-10 when it was stimulated with LPS compared to Mγ-Mϕ. Interestingly, M-Mϕ differentiated with glycolysis inhibitors (2-deoxy-D-glucose or DCA) produced significantly lower amount of IL-10 and lager amount of IL-6 compared to M-Mϕ differentiated without glycolysis inhibitors. Glycolysis inhibited M-Mϕ reduced the expression of regulatory Mϕ marker genes (MRC1 and CCL22) and exhibited distinct pattern of cell surface antigens (CD163, CD206, CD209 and HLA-DR) compared to M-Mϕ. DNA microarray analysis revealed that inhibition of glycolysis affects gene expression profiles during Mϕ differentiation. Our finding suggests that glycolysis plays key roles in the course of differentiation of Mϕ into IL-10 producing phenotype.