Format

Send to

Choose Destination
See comment in PubMed Commons below
J Reprod Immunol. 2004 Apr;61(2):67-77.

Indoleamine 2,3-dioxygenase expression is restricted to fetal trophoblast giant cells during murine gestation and is maternal genome specific.

Author information

1
Department of Medicine, Institute of Molecular Medicine and Genetics, Medical College of Georgia 1120, 15th Street, Augusta, GA 30912-2600, USA.

Abstract

Pharmacologic inhibition of indoleamine 2,3 dioxygenase (IDO) activity during murine pregnancy results in rejection of allogeneic fetuses by the maternal immune system. Here, we show that IDO expression is restricted to perinuclear regions of primary trophoblast giant cells (TGCs) of fetal origin at mid-gestation (E10.5). After placentation (E14), no IDO expression was detected at the maternal-fetal interface. Matings involving IDO-deficient females revealed that paternally inherited IDO alleles were inactive in primary TGCs, presumably due to paternal genome-specific gene inactivation. Allogeneic matings in which both parents were genetically IDO-deficient produced litters of normal sizes at normal rates compared to IDO-sufficient parental mice, implying that compensatory or redundant immunosuppressive mechanisms protected allogeneic fetuses during gestation in IDO-deficient mice. Consistent with this notion, treatment with IDO inhibitor did not affect allogeneic pregnancy rates when both parents were IDO-deficient, confirming that IDO was the relevant pharmacologic target of the IDO inhibitor in matings involving IDO-sufficient mice. Hence, IDO is a key immunosuppressive mechanism in normal murine pregnancies, and it is regulated entirely through maternally inherited fetal genes.

Comment in

PMID:
15063630
DOI:
10.1016/j.jri.2003.11.003
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center