Research Papers:

Hypoxia enhances indoleamine 2,3-dioxygenase production in dendritic cells

Xiang Song, Yan Zhang, Li Zhang, Wengang Song and Lixin Shi _

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Oncotarget. 2018; 9:11572-11580. https://doi.org/10.18632/oncotarget.24098

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Xiang Song1,2,*, Yan Zhang3,*, Li Zhang2, Wengang Song4 and Lixin Shi3

1Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China

2Comprehensive Ward, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China

3Department of Endocrinology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China

4Institute of Immunology, Taishan Medical University, Tai’an 271000, China

*These authors have contributed equally to this work

Correspondence to:

Lixin Shi, email: [email protected]

Keywords: dendritic cells; hypoxia; indoleamine 2,3-dioxygenase; adenosine; inflammation

Received: September 12, 2017     Accepted: January 03, 2018     Published: January 09, 2018


Hypoxia-associated metabolic reprogramming modulates the biological functions of many immune and non-immune cells, and affects immune response types and intensities. Adenosine and indoleamine 2,3-dioxygenase (IDO) are known immunosuppressors, and adenosine is a hypoxia-associated product. We investigated the impact of hypoxia on IDO production in dendritic cells (DCs). We found that hypoxia (1% O2) enhances IDO production in DCs, and this increase was dependent on the adenosine A3 receptor (A3R), but not A2aR or A2bR. A3R blockade during hypoxia inhibited IDO production in DCs, while A2bR blockade further enhanced IDO production. Activating A2aR had no effect on IDO production. Hypoxia (1% O2) upregulated CD86, CD274, HLA-DR, and CD54, and downregulated CD40 and CD83 in DCs as compared to normoxia (21% O2). IDO inhibition in hypoxia-conditioned DCs reversed MHC-II, CD86, CD54, and CD274 upregulation, but further downregulated CD40 and CD83. Our findings offer guidance for pharmacological administration of adenosine receptor agonists or antagonists with the goal of achieving immune tolerance or controlling insulin resistance and other metabolic disorders via IDO modulation.

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