PMID- 24954223
OWN - NLM
STAT- MEDLINE
DCOM- 20150515
LR  - 20211021
IS  - 2042-0226 (Electronic)
IS  - 1672-7681 (Print)
IS  - 1672-7681 (Linking)
VI  - 11
IP  - 5
DP  - 2014 Sep
TI  - Ly49 receptors activate angiogenic mouse DBA(+) uterine natural killer cells.
PG  - 467-76
LID - 10.1038/cmi.2014.44 [doi]
AB  - In humans, specific patterns of killer immunoglobulin-like receptors (KIRs) 
      expressed by uterine natural killer (uNK) cells are linked through HLA-C with 
      pregnancy complications (infertility, recurrent spontaneous abortion, 
      intrauterine growth restriction and preeclampsia). To identify mechanisms 
      underpinning the associations between NK cell activation and pregnancy success, 
      pregnancies were studied in mice with genetic knockdown (KD) of the MHC-activated 
      Ly49 receptor gene family. B6.Ly49(KD) pregnancies were compared to normal 
      control B6.Ly49(129) and C57BL/6 (B6) pregnancies. At mid-pregnancy (gestation 
      day (gd9.5)), overall uNK cell (TCRbeta(-)CD122(+)DBA(+)DX5(-) (DBA(+)DX5(-))) and 
      TCRbeta(-)CD122(+)DBA(-)DX5(+) (DBA(-)DX5(+))) frequencies in pregnant uterus were 
      similar between genotypes. Ly49(KD) lowered the normal frequencies of Ly49(+) uNK 
      cells from 90.3% to 47.8% in DBA(-)DX5(+) and 78.8% to 6.3% in DBA(+)DX5(-) uNK 
      cell subtypes. B6.Ly49(KD) matings frequently resulted in expanded blastocysts 
      that did not implant (subfertility). B6.Ly49(KD) mice that established pregnancy 
      had gestational lengths and litter sizes similar to controls. B6.Ly49(KD) 
      neonates, however, were heavier than controls. B6.Ly49(KD) implantation sites 
      lagged in early (gd6.5) decidual angiogenesis and were deficient in mid-pregnancy 
      (gd10.5) spiral arterial remodelling. Ultrastructural analyses revealed that 
      B6.Ly49(KD) uNK cells had impaired granulogenesis, while immunocytochemistry 
      revealed deficient vascular endothelial cell growth factor (VEGFA) production. 
      Perforin and IFNG expression were normal in B6.Ly49(KD) uNK cells. Thus, in 
      normal mouse pregnancies, Ly49 receptor signaling must promote implantation, 
      early decidual angiogenesis and mid-pregnancy vascular remodelling. Disturbances 
      in these functions may underlie the reported genetic associations between human 
      pregnancy complications and the inability of specific conceptus MHCs to engage 
      activating KIR on uNK cells.
FAU - Lima, Patricia D A
AU  - Lima PD
AD  - 1] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, ON K1N 6N5, Canada [2] Biomedical and Molecular Sciences, Queen's 
      University, Kingston, ON K7L 3N6, Canada.
FAU - Tu, Megan M
AU  - Tu MM
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, ON K1N 6N5, Canada.
FAU - Rahim, Mir Munir A
AU  - Rahim MM
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, ON K1N 6N5, Canada.
FAU - Peng, Annie R
AU  - Peng AR
AD  - 1] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, ON K1N 6N5, Canada [2] Biomedical and Molecular Sciences, Queen's 
      University, Kingston, ON K7L 3N6, Canada.
FAU - Croy, B Anne
AU  - Croy BA
AD  - Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, 
      Canada.
FAU - Makrigiannis, Andrew P
AU  - Makrigiannis AP
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, ON K1N 6N5, Canada.
LA  - eng
GR  - MOP 62841/Canadian Institutes of Health Research/Canada
GR  - MOP 77519/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140623
PL  - China
TA  - Cell Mol Immunol
JT  - Cellular & molecular immunology
JID - 101242872
RN  - 0 (HLA-C Antigens)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily A)
RN  - 0 (Ribosomal Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (ribosomal protein S19)
RN  - 0 (vascular endothelial growth factor A, mouse)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Embryo Implantation/genetics
MH  - Female
MH  - HLA-C Antigens/metabolism
MH  - Killer Cells, Natural/*immunology
MH  - Lymphocyte Activation
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NK Cell Lectin-Like Receptor Subfamily A/genetics/*metabolism
MH  - Neovascularization, Physiologic/genetics
MH  - Pregnancy
MH  - Ribosomal Proteins/metabolism
MH  - Signal Transduction
MH  - Uterus/*immunology
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
MH  - Vascular Remodeling/genetics
PMC - PMC4197209
EDAT- 2014/06/24 06:00
MHDA- 2015/05/16 06:00
PMCR- 2014/09/01
CRDT- 2014/06/24 06:00
PHST- 2014/05/02 00:00 [received]
PHST- 2014/05/14 00:00 [accepted]
PHST- 2014/06/24 06:00 [entrez]
PHST- 2014/06/24 06:00 [pubmed]
PHST- 2015/05/16 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - cmi201444 [pii]
AID - 10.1038/cmi.2014.44 [doi]
PST - ppublish
SO  - Cell Mol Immunol. 2014 Sep;11(5):467-76. doi: 10.1038/cmi.2014.44. Epub 2014 Jun 
      23.