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Mouse fetal growth restriction through parental and fetal immune gene variation and intercellular communications cascade.
Kaur, Gurman; Porter, Caroline B M; Ashenberg, Orr; Lee, Jack; Riesenfeld, Samantha J; Hofree, Matan; Aggelakopoulou, Maria; Subramanian, Ayshwarya; Kuttikkatte, Subita Balaram; Attfield, Kathrine E; Desel, Christiane A E; Davies, Jessica L; Evans, Hayley G; Avraham-Davidi, Inbal; Nguyen, Lan T; Dionne, Danielle A; Neumann, Anna E; Jensen, Lise Torp; Barber, Thomas R; Soilleux, Elizabeth; Carrington, Mary; McVean, Gil; Rozenblatt-Rosen, Orit; Regev, Aviv; Fugger, Lars.
  • Kaur G; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Porter CBM; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ashenberg O; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lee J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Riesenfeld SJ; Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
  • Hofree M; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Aggelakopoulou M; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA.
  • Subramanian A; Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Kuttikkatte SB; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Attfield KE; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Desel CAE; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Davies JL; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Evans HG; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Avraham-Davidi I; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Nguyen LT; University Department of Neurology, University Hospital Magdeburg, Magdeburg, Germany.
  • Dionne DA; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Neumann AE; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Jensen LT; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Barber TR; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Soilleux E; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Carrington M; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • McVean G; Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Rozenblatt-Rosen O; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Regev A; Department of Pathology, Tennis Court Rd, University of Cambridge, Cambridge, England.
  • Fugger L; Basic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD, USA.
Nat Commun ; 13(1): 4398, 2022 07 29.
Article en En | MEDLINE | ID: mdl-35906236
Fetal growth restriction (FGR) affects 5-10% of pregnancies, and can have serious consequences for both mother and child. Prevention and treatment are limited because FGR pathogenesis is poorly understood. Genetic studies implicate KIR and HLA genes in FGR, however, linkage disequilibrium, genetic influence from both parents, and challenges with investigating human pregnancies make the risk alleles and their functional effects difficult to map. Here, we demonstrate that the interaction between the maternal KIR2DL1, expressed on uterine natural killer (NK) cells, and the paternally inherited HLA-C*0501, expressed on fetal trophoblast cells, leads to FGR in a humanized mouse model. We show that the KIR2DL1 and C*0501 interaction leads to pathogenic uterine arterial remodeling and modulation of uterine NK cell function. This initial effect cascades to altered transcriptional expression and intercellular communication at the maternal-fetal interface. These findings provide mechanistic insight into specific FGR risk alleles, and provide avenues of prevention and treatment.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trofoblastos / Retardo del Crecimiento Fetal Tipo de estudio: Prognostic_studies Límite: Animals / Pregnancy Idioma: En Año: 2022 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trofoblastos / Retardo del Crecimiento Fetal Tipo de estudio: Prognostic_studies Límite: Animals / Pregnancy Idioma: En Año: 2022 Tipo del documento: Article