Dendritic cell-specific ICAM-3-grabbing nonintegrin expression on M2-polarized and tumor-associated macrophages is macrophage-CSF dependent and enhanced by tumor-derived IL-6 and IL-10

• Published in: The Journal of immunology (1950) 2011-02, Vol.186 (4), p.2192-2200
• Main Authors: Domínguez-Soto, Angeles, Sierra-Filardi, Elena, Puig-Kröger, Amaya, Pérez-Maceda, Blanca, Gómez-Aguado, Fernando, Corcuera, María Teresa, Sánchez-Mateos, Paloma, Corbí, Angel L
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Breast Neoplasms - immunology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Adhesion Molecules - biosynthesis; Cell Adhesion Molecules - genetics; Cell Differentiation - immunology; Cell Polarity - immunology; Cells, Cultured; Culture Media, Conditioned - pharmacology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Disease Progression; Gene Expression Regulation - immunology; Humans; Immunocompromised Host - genetics; Immunocompromised Host - immunology; Inflammation Mediators - metabolism; Inflammation Mediators - physiology; Interleukin-10 - physiology; Interleukin-6 - physiology; Lectins, C-Type - biosynthesis; Lectins, C-Type - genetics; Macrophage Colony-Stimulating Factor - physiology; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Melanoma, Experimental - immunology; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Neoplasm Proteins - physiology; Receptors, Cell Surface - biosynthesis; Receptors, Cell Surface - genetics; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1000475

Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN; CD209) is a human pathogen-attachment C-type lectin with no obvious murine ortholog and for which ligation leads to enhanced anti-inflammatory cytokine release and altered proinflammatory cytokine production. Although induced by IL-4 in monocytes and considered as a DC marker, DC-SIGN expression on human APCs under homeostatic conditions is so far unexplained. We report in this study that M-CSF enhances DC-SIGN expression on in vitro derived anti-inflammatory macrophages and that M-CSF mediates the induction of DC-SIGN by fibroblast- and tumor cell-conditioned media. The M-CSF-inducible DC-SIGN expression along monocyte-to-macrophage differentiation is dependent on JNK and STAT3 activation, potentiated by STAT3-activating cytokines (IL-6, IL-10), and abrogated by the M1-polarizing cytokine GM-CSF. In pathological settings, DC-SIGN expression is detected in tumor tissues and on ex vivo-isolated CD14(+) CD163(+) IL-10-producing tumor-associated macrophages. Importantly, DC-SIGN Abs reduced the release of IL-10 from macrophages exposed to Lewis(x)-expressing SKBR3 tumor cells. These results indicate that DC-SIGN is expressed on both wound-healing (IL-4-dependent) and regulatory (M-CSF-dependent) alternative (M2) macrophages and that DC-SIGN expression on tumor-associated macrophages might help tumor progression by contributing to the maintenance of an immunosuppressive environment.