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
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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. / Blois, Sandra; Tometten, Mareike; Kandil, Judith; Hagen, Evelin; Klapp, Burghard F; Margni, Ricardo A; Arck, Petra C.
In: J IMMUNOL, Vol. 174, No. 4, 15.02.2005, p. 1820-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 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
AU - Blois, Sandra
AU - Tometten, Mareike
AU - Kandil, Judith
AU - Hagen, Evelin
AU - Klapp, Burghard F
AU - Margni, Ricardo A
AU - Arck, Petra C
PY - 2005/2/15
Y1 - 2005/2/15
N2 - 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.
AB - 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.
KW - Animals
KW - Antibodies, Blocking/pharmacology
KW - Cell Differentiation/immunology
KW - Cell Lineage/immunology
KW - Cell Movement/immunology
KW - Decidua/enzymology
KW - Dendritic Cells/cytology
KW - Female
KW - Graft Rejection/immunology
KW - Immune Tolerance/immunology
KW - Intercellular Adhesion Molecule-1/biosynthesis
KW - Lymphocyte Count
KW - Lymphocyte Function-Associated Antigen-1/biosynthesis
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred CBA
KW - Mice, Inbred DBA
KW - Pregnancy
KW - Pregnancy Proteins/antagonists & inhibitors
KW - Stress, Physiological/immunology
KW - Th1 Cells/cytology
KW - Th2 Cells/cytology
KW - Tryptophan Oxygenase/antagonists & inhibitors
KW - Up-Regulation/immunology
KW - Uterus/cytology
U2 - 10.4049/jimmunol.174.4.1820
DO - 10.4049/jimmunol.174.4.1820
M3 - SCORING: Journal article
C2 - 15699108
VL - 174
SP - 1820
EP - 1829
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 4
ER -