Indoleamine 2,3-dioxygenase: distribution and function in the developing human placenta.
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.
Kudo
Yoshiki
Y
Department of Human Anatomy and Genetics, University of Oxford, Oxford, UK. yoshkudo@hiroshima-u.ac.jp
Boyd
C A R
CA
Spyropoulou
Isabella
I
Redman
C W G
CW
Takikawa
Osamu
O
Katsuki
Takafumi
T
Hara
Tetsuaki
T
Ohama
Koso
K
Sargent
I L
IL
D000998:Antiviral Agents / Q000494:pharmacology; D001755:Blastocyst / Q000201:enzymology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D046508:Culture Techniques; D005321:Extraembryonic Membranes / Q000201:enzymology* / Q000276:immunology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000276:immunology / Q000502:physiology; D010920:Placenta / Q000196:embryology / Q000201:enzymology* / Q000276:immunology; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
D000998:Antiviral Agents; C028129:tryptophan methyl ester; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase