title: A review of trafficking and activation of uterine natural killer cells.
abstract: OBJECTIVE
  Enrichment of uterine natural killer (uNK) cells occurs during pregnancy in many species. However, functions of uNK cells and regulation of their uterine homing are not fully defined. In mice and women, uNK cells contribute to angiogenesis, a role reviewed here and now addressed in a mammal with an alternative placental type.
  
  
  METHODS
  To address lymphocyte functions, RNA from murine or porcine endometrium and lymphocytes purified from endometrium were analyzed using real-time or reverse transcription PCR. To address homing potential, human blood CD56(+) lymphocytes were evaluated using both RNA and functional adhesion to endothelium presented under shear force in frozen sections of gestation day 7 C57Bl/6J implantation sites. Women were serially sampled over a menstrual cycle or a clinical preparatory cycle for embryo transfer.
  
  
  RESULTS
  Activation of murine uNK cells is associated with much greater increases in transcription for Eomes than for T-bet (Tbx21). Lymphocytes from normal porcine implantation sites transcribe vascular endothelial growth factor, placental growth factor, interferon-gamma and hypoxia-inducible factor (HIF)-1alpha. In fertile women, increases in L-selectin- and alpha4-integrin-mediated interactions between CD56(+) cells and endothelium occur at luteinizing hormone (LH) surge (cycling women) to oocyte pick up or embryo transfer, then return to pre-LH levels.
  
  
  CONCLUSIONS
  Uterine lymphocytes may universally promote pregnancy-associated endometrial angiogenesis. Recruitment of uNK precursor cells from blood appears to occur in a window promoted by rising plasma estrogen and LH and limited by rising progesterone.
authors.affiliation: Department of Pediatrics, University of Western Ontario, London, Canada.
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: van den Heuvel
authors.forename: Xuemei
authors.initials: X
authors.lastname: Xie
authors.forename: Chandrakant
authors.initials: C
authors.lastname: Tayade
authors.forename: Crystal
authors.initials: C
authors.lastname: Peralta
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.forename: Sean
authors.initials: S
authors.lastname: Leonard
authors.forename: Valdemar A
authors.initials: VA
authors.lastname: Paffaro
authors.forename: Abdol K
authors.initials: AK
authors.lastname: Sheikhi
authors.forename: Coral
authors.initials: C
authors.lastname: Murrant
authors.forename: Barbara Anne
authors.initials: BA
authors.lastname: Croy
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D011247:Pregnancy; D013552:Swine; D014599:Uterus / Q000166:cytology* / Q000276:immunology*