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Indoleamine 2,3-dioxygenase: distribution and function in the developing human placenta.

Yoshiki Kudo·C A R Boyd·Isabella Spyropoulou·C W G Redman·Osamu Takikawa·Takafumi Katsuki·Tetsuaki Hara·Koso Ohama·I L Sargent
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Abstract

Studies in mice have suggested that the placenta is protected from immune rejection by maternal T cells by means of localised indoleamine 2,3-dioxygenase dependent depletion of tryptophan. To determine whether such mechanisms might operate in the human placenta, we have studied the physiological importance of human placental indoleamine 2,3-dioxygenase immunohistochemically and functionally. Indoleamine 2,3-dioxygenase is detectable immunohistochemically from day 6 human blastocysts and thereafter throughout pregnancy in syncytiotrophoblasts, extravillous cytotrophoblasts and macrophages in the villous stroma and in the fetal membranes. Interferon-gamma added to villous explants markedly stimulates indoleamine 2,3-dioxygenase protein expression in macrophages. Indoleamine 2,3-dioxygenase-mediated tryptophan degradation in the first trimester villous and decidual tissue explants is stimulated by interferon-gamma and inhibited by 1-methyl-tryptophan (an inhibitor of indoleamine 2,3-dioxygenase). Peripheral blood mononuclear cell proliferation is controlled by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. These results suggest the cellular basis of a mechanism present at the human maternal-fetal interface involved in regulating the maternal immune response to conceptus.

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Antiviral AgentsBlastocystCell DivisionCulture TechniquesExtraembryonic MembranesFemaleGene Expression Regulation, DevelopmentalHumansImmunohistochemistryInterferon-gammaLeukocytes, MononuclearLymphocyte ActivationMacrophagesMaternal-Fetal ExchangePlacentaPregnancyT-LymphocytesTryptophanTryptophan OxygenaseJournal ArticleResearch Support, Non-U.S. Gov't

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Yoshiki Kudo, C A R Boyd, Isabella Spyropoulou, C W G Redman, Osamu Takikawa, Takafumi Katsuki, Tetsuaki Hara, Koso Ohama, I L Sargent. 2004. Indoleamine 2,3-dioxygenase: distribution and function in the developing human placenta.. https://doi.org/10.1016/j.jri.2003.11.004

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