The role of indoleamine 2,3-dioxygenase (IDO) in immune tolerance: focus on 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.
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, PR China; Shijiazhuang Center for Disease Control and Prevention, Shijiazhuang, PR China.
Xian-Feng
XF
Wang
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, PR China.
Hong-Sheng
HS
Wang
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, PR China.
Hao
H
Wang
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, PR China.
Fan
F
Zhang
Department of Obstetrics and Gynecology, Beijing Anzhen Hospital, Capital Medical University, Beijing, PR China.
Ke-Fang
KF
Wang
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, PR China.
Qiang
Q
Guo
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, PR China.
Ge
G
Zhang
Department of Pharmacology, College of Pharmacy, Jinan University, Guangzhou, PR China. Electronic address: csh5689@sina.com.
Shao-Hui
SH
Cai
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, PR China. Electronic address: dujun@mail.sysu.edu.cn.
Jun
J
Du
D002454:Cell Differentiation / Q000276:immunology*; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007155:Immunologic Factors / Q000235:genetics / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis; D053765:Interleukin-12 Subunit p35 / Q000096:biosynthesis; D007938:Leukemia / Q000276:immunology; D008264:Macrophages / Q000145:classification / Q000276:immunology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D054400:Receptors, CCR7 / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis
C515370:CCR7 protein, human; C527276:CXCR4 protein, human; C508609:IL10 protein, human; D007155:Immunologic Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053765:Interleukin-12 Subunit p35; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D016753:Interleukin-10
Cancer therapy; Immune tolerance; Indoleamine 2,3-dioxygenase (IDO); M1; M2