DC within the pregnant mouse uterus influence growth and functional properties of uterine NK cells

• Published in: European journal of immunology 2009-08, Vol.39 (8), p.2203-2214
• Main Authors: Karsten, Christian M, Behrends, Jochen, Wagner, Arnika K, Fuchs, Franca, Figge, Julia, Schmudde, Inken, Hellberg, Lars, Kruse, Andrea
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antibodies, Monoclonal - pharmacology; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; CD11b Antigen - metabolism; CD11c Antigen - metabolism; Cell Adhesion Molecules - immunology; Cell Movement - drug effects; Dendritic Cells - cytology; Dendritic Cells - metabolism; Dendritic Cells - transplantation; Female; Integrin beta Chains - genetics; Integrin beta Chains - metabolism; Integrins; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Interferon-gamma - metabolism; Interleukin-12 - genetics; Interleukin-12 - metabolism; Interleukin-12 - pharmacology; Interleukin-15 - genetics; Interleukin-15 - metabolism; Interleukin-15 - pharmacology; Killer Cells, Natural - cytology; Killer Cells, Natural - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NK cells; P-Selectin - genetics; P-Selectin - metabolism; Pregnancy; Reproductive immunology; Reverse Transcriptase Polymerase Chain Reaction; Rodent; Uterus - cytology; Uterus - immunology; Uterus - metabolism
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200838844

The vascular addressins mucosal addressin cell adhesion molecule-1, P-selectin and ICAM-1 permit α₄β₇-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 β7-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 β7-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-γ 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.