Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells
| Autor: | Annie R Peng, B. Anne Croy, Mir Munir A. Rahim, Patricia D.A. Lima, Andrew P. Makrigiannis, Megan M. Tu |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Ribosomal Proteins Vascular Endothelial Growth Factor A medicine.medical_specialty Angiogenesis Immunology Uterus Neovascularization Physiologic HLA-C Antigens Biology Vascular Remodeling Lymphocyte Activation Preeclampsia Vascular remodelling in the embryo Mice Pregnancy Internal medicine medicine Immunology and Allergy Conceptus Animals Embryo Implantation Receptor Mice Knockout medicine.disease Killer Cells Natural Mice Inbred C57BL Vascular endothelial growth factor A Infectious Diseases medicine.anatomical_structure Endocrinology Animals Newborn embryonic structures Female NK Cell Lectin-Like Receptor Subfamily A Research Article Signal Transduction |
| Popis: | 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 (TCRβ(-)CD122(+)DBA(+)DX5(-) (DBA(+)DX5(-))) and TCRβ(-)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. |
| Databáze: | OpenAIRE |
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