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The role of indoleamine 2,3-dioxygenase (IDO) in immune tolerance: Focus on macrophage polarization of THP-1 cells

机译:吲哚胺2,3-双加氧酶(IDO)在免疫耐受中的作用:专注于THP-1细胞的巨噬细胞极化

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Macrophages can be divided into two groups as M1 and M2 phenotype. Our results and other groups revealed that IFN-γ can up-regulate the IDO expression and differentiate THP-1 cells to M1 phenotype. Therefore we hypothesized that IDO may play potential roles in macrophage differentiation. Interesting, our results indicated that the ectopic IDO increases the expression of M2 markers such as IL-10 and CXCR4 while decreases the M1 markers such as CCR7 and IL-12p35. In contrast, the knockdown of IDO expression in THP-1 cells resulted in increased M1 markers and lower M2 markers. Our results suggested that the expression intensity of IDO modulates macrophages differentiation. These finding support the counter-regulatory role for IDO with regarding to the polarization of macrophages to restrain excessive or inappropriate immune activation in inflammatory or tumor microenvironment. It throws new light on the mechanisms about the immunosuppressive effect of IDO in tumor or inflammatory diseases.
机译:巨噬细胞可分为M1和M2表型两类。我们的结果和其他研究小组表明,IFN-γ可以上调IDO表达并使THP-1细胞分化为M1表型。因此,我们假设IDO可能在巨噬细胞分化中发挥潜在作用。有趣的是,我们的结果表明异位IDO增加了M2标记物(如IL-10和CXCR4)的表达,同时降低了M1标记物(如CCR7和IL-12p35)。相反,在THP-1细胞中IDO表达的敲低导致M1标记增加而M2标记降低。我们的结果表明IDO的表达强度调节巨噬细胞分化。这些发现支持IDO在巨噬细胞极化方面的反调节作用,以抑制炎性或肿瘤微环境中过度或不适当的免疫活化。它为IDO在肿瘤或炎性疾病中的免疫抑制作用机理提供了新的思路。

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