title: Intercellular adhesion molecule-1/LFA-1 cross talk is a proximate mediator capable of disrupting immune integration and tolerance mechanism at the feto-maternal interface in murine pregnancies.
abstract: Our understanding why a woman's immune system does not reject her histoincompatible fetus is still very limited. Distinct insights into the mechanisms involved in pregnancy maintenance may help us to prevent pregnancy complications, e.g., miscarriages or pre-eclampsia. Immune integration and tolerance at the feto-maternal interface appear to be indispensable for successful pregnancy maintenance. Little is known about the cross talk between ICAM-1, expressed on epithelium, endothelium, and APC, and its ligand, LFA-1, at the feto-maternal interface. However, based on the role of ICAM-1/LFA-1 in allograft acceptance or rejection upon transplantation, adhesion molecules are likely to interfere with successful pregnancy outcome. In this study, we tested the hypothesis that ICAM-1/LFA-1 pathways may be involved in pregnancy rejection in murine models. By blocking ICAM-1/LFA-1-mediated intercellular adhesion events, we show that fetal immune acceptance is restored in challenged pregnancies (e.g., upon exposure to sound stress), and adoptive transfer of LFA-1 cells into pregnant mice induces rejection only in abortion-prone mouse models. ICAM-1/LFA-1 cross talk leads to increased recruitment of proinflammatory cells to the implantation site, promotes dendritic cell maturation in the decidua, and subsequently induces additional local Th1 polarization via mature dendritic cells. Furthermore, our observations clearly point out that mechanisms of fetal tolerance, e.g., indoleamine 2,3-dioxygenase expression, presence of CD4+CD25bright regulatory T cells, and synthesis of asymmetric Abs, are ICAM-1/LFA-1 dependent. Hence, our data shed light on a hierarchical network of immune integration at the feto-maternal interface, in which ICAM-1/LFA-1 cross talk is clearly a proximate mediator capable of disrupting successful pregnancy maintenance.
authors.affiliation: Charité, University Medicine Berlin, Berlin, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Blois
authors.forename: Mareike
authors.initials: M
authors.lastname: Tometten
authors.forename: Judith
authors.initials: J
authors.lastname: Kandil
authors.forename: Evelin
authors.initials: E
authors.lastname: Hagen
authors.forename: Burghard F
authors.initials: BF
authors.lastname: Klapp
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Margni
authors.forename: Petra C
authors.initials: PC
authors.lastname: Arck
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003656:Decidua / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007108:Immune Tolerance / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D018655:Lymphocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D013312:Stress, Physiological / Q000276:immunology / Q000517:prevention & control; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology; D014599:Uterus / Q000166:cytology / Q000276:immunology
chemical_list: D019138:Antibodies, Blocking; D016169:Lymphocyte Function-Associated Antigen-1; D011257:Pregnancy Proteins; D018799:Intercellular Adhesion Molecule-1; D014366:Tryptophan Oxygenase