Vascular Endothelial Expression of Indoleamine 2,3-Dioxygenase 1 Forms a Positive Gradient towards the Feto-Maternal Interface

Abstract

We describe the distribution of indoleamine 2,3-dioxygenase 1 (IDO1) in vascular endothelium of human first-trimester and term placenta. Expression of IDO1 protein on the fetal side of the interface extended from almost exclusively sub-trophoblastic capillaries in first-trimester placenta to a nearly general presence on villous vascular endothelia at term, including also most bigger vessels such as villous arteries and veins of stem villi and vessels of the chorionic plate. Umbilical cord vessels were generally negative for IDO1 protein. In the fetal part of the placenta positivity for IDO1 was restricted to vascular endothelium, which did not co-express HLA-DR. This finding paralleled detectability of IDO1 mRNA in first trimester and term tissue and a high increase in the kynurenine to tryptophan ratio in chorionic villous tissue from first trimester to term placenta. Endothelial cells isolated from the chorionic plate of term placenta expressed IDO1 mRNA in contrast to endothelial cells originating from human umbilical vein, iliac vein or aorta. In first trimester decidua we found endothelium of arteries rather than veins expressing IDO1, which was complementory to expression of HLA-DR. An estimation of IDO activity on the basis of the ratio of kynurenine and tryptophan in blood taken from vessels of the chorionic plate of term placenta indicated far higher values than those found in the peripheral blood of adults. Thus, a gradient of vascular endothelial IDO1 expression is present at both sides of the feto-maternal interface.

The Placenta in Toxicology. Part I

“…The differences between human and cynomolgus monkey HLA-G expression cannot be conclusively explained and may at least in part correlate with different trophoblast-decidua invasion patterns in both species ( Figure 1E-F). Syncytiotrophoblast HLA-G immunoreactivity, with an obvious apical cytoplasmic stain was mentioned before in more immature (GD 36-42) NHP placentae (Bondarenko et al 2009), but has in our study also been detected in more advanced stages of NHP gestation.…”

Extensive Profiling of the Expression of the Indoleamine 2,3-Dioxygenase 1 Protein in Normal and Tumoral Human Tissues

“…TDO2 is expressed constitutively in the liver, where it acts as the main regulator of systemic tryptophan levels. The nonhomologous IDO1 enzyme is expressed in the placenta, the mucosal and lymphoid tissues, and inflammatory lesions (2,3). In the latter two, it is expressed primarily by antigen-presenting cells (APC), mainly dendritic cells (DC) and macrophages, and in cells exposed to IFNg and other proinflammatory stimuli.…”

“…IDO1 immunoreactivity has been reported in trophoblast cells, macrophages, and mesenchymal or endothelial cells, depending on the study (3,(26)(27)(28)(29)(30)(31). In human tumors, most published studies have focused on IDO1 expression and prognostic significance in individual tumor types.…”

Tumoral Immune Resistance Mediated by Enzymes That Degrade Tryptophan

“…IDO1 mRNA and protein are not expressed or are very weakly expressed in most healthy human tissues with the exception of the placenta, the mucosa of the female genital tract, the lungs, and the lymphoid organs (14,15). In the placenta, IDO1 is found in endothelial cells of blood vessels present both at the fetal and the maternal interface (14,16). This contrasts with mouse Ido1, which appears to be mainly expressed in trophoblast cells (17,18).…”

“…The functional consequence of this differential cellular expression, particularly in terms of fetal resistance against maternal immune rejection, is not known. Placental IDO1 is enzymatically active, as indicated by the increased kynurenine-to-tryptophan gradient in umbilical cord blood (16). How fetal development copes with reduced tryptophan is another mystery.…”