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

•IFN-γ differentiates THP-1 cells to M1-type macrophages and upregulates IDO expression.•Over expression of IDO promotes M2-polarized THP-1 macrophages.•Effects of IDO-knockdown on the macrophage polarization of THP-1 cells. Macrophages can be divided into two groups as M1 and M2 phenotype. Our resu...

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Veröffentlicht in:Cellular immunology 2014-05, Vol.289 (1-2), p.42-48
Hauptverfasser: Wang, Xian-Feng, Wang, Hong-Sheng, Wang, Hao, Zhang, Fan, Wang, Ke-Fang, Guo, Qiang, Zhang, Ge, Cai, Shao-Hui, Du, Jun
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container_end_page 48
container_issue 1-2
container_start_page 42
container_title Cellular immunology
container_volume 289
creator Wang, Xian-Feng
Wang, Hong-Sheng
Wang, Hao
Zhang, Fan
Wang, Ke-Fang
Guo, Qiang
Zhang, Ge
Cai, Shao-Hui
Du, Jun
description •IFN-γ differentiates THP-1 cells to M1-type macrophages and upregulates IDO expression.•Over expression of IDO promotes M2-polarized THP-1 macrophages.•Effects of IDO-knockdown on the macrophage polarization of THP-1 cells. 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.
doi_str_mv 10.1016/j.cellimm.2014.02.005
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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. 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subjects Cancer therapy
Cell Differentiation - immunology
Cell Line, Tumor
Cell Polarity - immunology
Humans
Immune tolerance
Immune Tolerance - immunology
Immunologic Factors - genetics
Immunologic Factors - immunology
Indoleamine 2,3-dioxygenase (IDO)
Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics
Indoleamine-Pyrrole 2,3,-Dioxygenase - immunology
Interleukin-10 - biosynthesis
Interleukin-12 Subunit p35 - biosynthesis
Leukemia - immunology
Macrophages - classification
Macrophages - immunology
Receptors, CCR7 - biosynthesis
Receptors, CXCR4 - biosynthesis
RNA Interference
RNA, Messenger - biosynthesis
RNA, Small Interfering
title The role of indoleamine 2,3-dioxygenase (IDO) in immune tolerance: Focus on macrophage polarization of THP-1 cells
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