Abstract
The vascular addressins mucosal addressin cell adhesion molecule-1, P-selectin and ICAM-1 permit alpha(4)beta(7)-integrin-expressing DC, especially those of the myeloid lineage (CD11c(+)CD11b(+) DC), to access the pregnant mouse uterus. Injection of blocking monoclonal antibodies against mucosal addressin cell adhesion molecule-1 in P-selectin(-/-) mice or experimental approaches with beta7-integrin(-/-) or ICAM-1(-/-) mice revealed that limited access or absence of CD11c(+)CD11b(+) DC at the maternal/fetal interface negatively affects the frequency, size and functional properties of uterine NK (uNK) cells. Adoptive transfer of DC obtained from WT mice into beta7-integrin(-/-) mice abrogates these effects and emphasizes the importance of DC in uNK cell differentiation. Interestingly, those implantation sites lacking CD11c(+)CD11b(+) DC are characterized by decreased IL-15 and IL-12 mRNA and/or protein levels. Chronic administration of IL-15 in these mice gives rise to uNK cell numbers and size comparable to those of WT mice, whereas additional injection of IL-12 positively affects the IFN-gamma expression of uNK cells. Real-time RT-PCR and protein arrays performed with isolated uterine DC underline the role of DC as a source of IL-15 and IL-12 in the pregnant mouse uterus.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Antibodies, Monoclonal / pharmacology
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Bone Marrow Cells / cytology
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Bone Marrow Cells / metabolism
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CD11b Antigen / metabolism
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CD11c Antigen / metabolism
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Cell Adhesion Molecules / immunology
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Cell Movement / drug effects
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Dendritic Cells / cytology
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Dendritic Cells / metabolism*
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Dendritic Cells / transplantation
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Female
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Integrin beta Chains / genetics
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Integrin beta Chains / metabolism
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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Interferon-gamma / metabolism
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Interleukin-12 / genetics
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Interleukin-12 / metabolism
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Interleukin-12 / pharmacology
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Interleukin-15 / genetics
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Interleukin-15 / metabolism
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Interleukin-15 / pharmacology
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Killer Cells, Natural / cytology
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Killer Cells, Natural / metabolism*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mucoproteins
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P-Selectin / genetics
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P-Selectin / metabolism
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Pregnancy
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Reverse Transcriptase Polymerase Chain Reaction
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Uterus / cytology
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Uterus / immunology
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Uterus / metabolism*
Substances
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Antibodies, Monoclonal
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CD11b Antigen
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CD11c Antigen
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Cell Adhesion Molecules
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Integrin beta Chains
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Interleukin-15
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Madcam1 protein, mouse
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Mucoproteins
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P-Selectin
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integrin beta7
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Intercellular Adhesion Molecule-1
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Interleukin-12
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Interferon-gamma