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The journal of immunology : official journal of the American Association of Immunologists v.198 no.3, 2017년, pp.1345 - 1356   SCI SCIE
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Immune Modifications in Fetal Membranes Overlying the Cervix Precede Parturition in Humans

Marcellin, Louis (INSERM, U1016, Institut Cochin, 75014 Paris, France ) ; Schmitz, Thomas (Service de Gynécologie Obstétrique, Hôpital Robert Debré, Assistance Publique–Hôpitaux de Paris, 75014 Paris, France ) ; Messaoudene, Meriem (INSERM, U1016, Institut Cochin, 75014 Paris, France ) ; Chader, Driss (INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, 75013 Paris, France ) ; Parizot, Christophe (INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, 75013 Paris, France ) ; Jacques, Sébastien (INSERM, U1016, Institut Cochin, 75014 Paris, France ) ; Delaire, Jérémy (INSERM, U1016, Institut Cochin, 75014 Paris, France ) ; Gogusev, Jean (INSERM, U1016, Institut Cochin, 75014 Paris, France ) ; Schmitt, Alain (INSERM, U1016, Institut Cochin, 75014 Paris, France ) ; Lesaffre, Corinne (INSERM, U1016, Institut Cochin, 75014 Paris, France ) ; Breuiller-Fouché, Michelle (INSERM, U1016, Institut Cochin, 75014 Paris, France ) ; Caignard, Anne (INSERM, U1016, Institut Cochin, 75014 Paris, France ) ; Vaiman, Daniel (INSERM, U1016, Institut Cochin, 75014 Paris, France ) ; Goffinet, François (Faculté ) ; Cabrol, Dominique (de Médecine, Université ) ; Gorochov, Guy (Paris Descartes, 75015 Paris, France ) ; Méhats, Céline (Faculté ) ;
  • 초록  

    In humans, parturition is currently viewed as an intrauterine outbreak of inflammation, accompanied by a massive release of proinflammatory cytokines at the maternal–fetal interface that comprises the maternal decidua, placenta, and fetal membranes. At term, fetal membranes overlying the cervix, the future site of rupture, show altered morphology and are termed the zone of altered morphology (ZAM). These alterations occur in normal fetal membranes during late pregnancy, in preparation for labor. In this study, transcriptome, flow cytometry, electron microscopy, and immunohistochemistry analyses collectively highlight a local shift in gene expression and lymphocyte activation in the ZAM. Just before labor, we show that highly polymorphic HLA-A, -B, and -C determinants of fetal origin are selectively exposed in the ZAM to the maternal immune system. A graft rejection-like program occurs in the ZAM, which involves 1) the activation of cytotoxic decidual NK cells, and 2) the decline of decidual immunotolerant M2-like macrophages. Comparison with a prior cohort of fetal membranes shows that acute inflammation only takes place after these first steps of immune modifications. Our results therefore strongly argue in favor of local immune remodeling at the onset of parturition.


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