DC within the pregnant mouse uterus influence growth and functional properties of uterine NK cells.
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.
Karsten
Christian M
CM
Institute of Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
Behrends
Jochen
J
Wagner
Arnika K
AK
Fuchs
Franca
F
Figge
Julia
J
Schmudde
Inken
I
Hellberg
Lars
L
Kruse
Andrea
A
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D005260:Female; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009088:Mucoproteins; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D039521:CD11c Antigen; D015815:Cell Adhesion Molecules; D039641:Integrin beta Chains; D019409:Interleukin-15; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D019007:P-Selectin; C091368:integrin beta7; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D007371:Interferon-gamma