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

Astrid Blaschitz,Osamu Takikawa,Petra Maschke,Peter Sedlmayr,Martin Gauster,Dietmar Fuchs,Ingrid Lang,Eva Karpf,Gottfried Dohr,Michael G Schimek,Daniela Ulrich,Lucienne Chatenoud

doi:10.1371/journal.pone.0021774

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.

Highlights

Pregnancy implicates a state of peaceful coexistence between hemiallogeneic tissues of the mother and the fetus
In villous chorion of tissue samples collected between the 6th and the 11th week of gestation expression of IDO1 was in most cases restricted to capillaries immediately below the trophoblastic layer (Fig.1a)
In extension of our previous observation of expression of IDO1 in the vascular endothelium of the decidua and the chorionic villi [7], we here report findings regarding the distribution of expression of IDO1 in the vasculature of the placenta

Summary

Introduction

Pregnancy implicates a state of peaceful coexistence between hemiallogeneic tissues of the mother and the fetus. Interest in the role of the tryptophan-degrading enzyme indoleamine 2,3dioxygenase in the context of feto-maternal tolerance and in immunosuppression in general was aroused more than ten years ago [1,2]. While placental expression of indoleamine 2,3dioxygenase (IDO) may not necessarily be a prerequisite for the tolerance-mediating role of the enzyme, most studies have focused on investigations of the direct cellular interfaces between mother and fetus, which is located in the decidua basalis, where the fetally derived invading trophoblast may be recognized and tolerated by the maternal uterine immune system [3] and the huge surface of syncytiotrophoblast which covers the placental villous trees and separates the maternal and fetal blood circulations from each other. IDO displays antimicrobial and antiviral effects by reducing the availability of the essential amino acid tryptophan in the inflammatory environment [9,10]

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Conclusion