The dominant lymphocytes in human and murine implantation sites are transient, pregnancy-associated uterine natural killer (uNK) cells. These cells are a major source of interferon (IFN)-γ. Implantation sites in mice lacking uNK cells (alymphoid recombinase activating gene [RAG]-2−/− common cytokine receptor chain γ [γc]−/−) or IFN-γ signaling (IFN-γ−/− or IFN-γRα−/−) fail to initiate normal pregnancy-induced modification of decidual arteries and display hypocellularity or necrosis of decidua. To investigate the functions of uNK cell–derived IFN-γ during pregnancy, RAG-2−/−γc−/− females were engrafted with bone marrow from IFN-γ−/− mice, IFN-γ signal-disrupted mice (IFN-γRα−/− or signal transducer and activator of transcription [Stat]-1−/−), or from mice able to establish normal uNK cells (severe combined immunodeficient [SCID] or C57BL/6). Mated recipients were analyzed at midgestation. All grafts established uNK cells. Grafts from IFN-γ−/− mice did not reverse host vascular or decidual pathology. Grafts from all other donors promoted modification of decidual arteries and decidual cellularity. Grafts from IFN-γRα−/− or Stat-1−/− mice overproduced uNK cells, all of which were immature. Grafts from IFN-γ−/−, SCID, or C57BL/6 mice produced normal, mature uNK cells. Administration of murine recombinant IFN-γ to pregnant RAG-2−/−γc−/− mice initiated decidual vessel modification and promoted decidual cellularity in the absence of uNK cells. These in vivo findings strongly suggest that uNK cell–derived IFN-γ modifies the expression of genes in the uterine vasculature and stroma, which initiates vessel instability and facilitates pregnancy-induced remodeling of decidual arteries.
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17 July 2000
Article|
July 17 2000
Interferon γ Contributes to Initiation of Uterine Vascular Modification, Decidual Integrity, and Uterine Natural Killer Cell Maturation during Normal Murine Pregnancy
Ali A. Ashkar,
Ali A. Ashkar
aDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1
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James P. Di Santo,
James P. Di Santo
bDepartment d' Immunologie, Institut Pasteur, 75724 Paris, France
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B. Anne Croy
B. Anne Croy
aDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1
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Ali A. Ashkar
aDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1
James P. Di Santo
bDepartment d' Immunologie, Institut Pasteur, 75724 Paris, France
B. Anne Croy
aDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1
Abbreviations used in this paper: BM, bone marrow; BV, blood vessels; gd, gestation day; MLAp, mesometrial lymphoid aggregate of pregnancy; PAS, periodic acid-Schiff; RAG, recombinase activating gene; Stat, signal transducer and activator of transcription; u, uterine.
Received:
March 29 2000
Revision Requested:
May 15 2000
Accepted:
May 17 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 192 (2): 259–270.
Article history
Received:
March 29 2000
Revision Requested:
May 15 2000
Accepted:
May 17 2000
Citation
Ali A. Ashkar, James P. Di Santo, B. Anne Croy; Interferon γ Contributes to Initiation of Uterine Vascular Modification, Decidual Integrity, and Uterine Natural Killer Cell Maturation during Normal Murine Pregnancy. J Exp Med 17 July 2000; 192 (2): 259–270. doi: https://doi.org/10.1084/jem.192.2.259
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