| First Author | Ashkar AA | Year | 2000 |
| Journal | J Exp Med | Volume | 192 |
| Issue | 2 | Pages | 259-70 |
| PubMed ID | 10899912 | Mgi Jnum | J:63645 |
| Mgi Id | MGI:1861330 | Doi | 10.1084/jem.192.2.259 |
| Citation | Ashkar AA, et al. (2000) Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy [see comments]. J Exp Med 192(2):259-70 |
| abstractText | 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)-gamma. Implantation sites in mice lacking uNK cells (alymphoid recombinase activating gene [RAG]-2(-/)- common cytokine receptor chain gamma [gamma(c)](-/)-) or IFN-gamma signaling (IFN-gamma(-/)- or IFN-gammaRalpha(-/)-) 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-gamma during pregnancy, RAG-2(-/)-gamma(c)(-/)- females were engrafted with bone marrow from IFN-gamma(-/)- mice, IFN-gamma signal-disrupted mice (IFN-gammaRalpha(-/)- 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-gamma(-/)- 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-gammaRalpha(-/)- or Stat-1(-/)- mice overproduced uNK cells, all of which were immature. Grafts from IFN-gamma(-/)-, SCID, or C57BL/6 mice produced normal, mature uNK cells. Administration of murine recombinant IFN-gamma to pregnant RAG-2(-/)-gamma(c)(-/)- 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-gamma modifies the expression of genes in the uterine vasculature and stroma, which initiates vessel instability and facilitates pregnancy-induced remodeling of decidual arteries. |
