IL-10-Conditioned Dendritic Cells, Decommissioned for Recruitment of Adaptive Immunity, Elicit Innate Inflammatory Gene Products in Response to Danger Signals

Kathleen Nolan, Kathleen F. Nolan, Victoria Strong, Dulce Soler, Paul J. Fairchild, Stephen P. Cobbold, Ruth Croxton, Jose Angel Gonzalo, Ana Rubio, Meghan Wells, Herman Waldmann

    Research output: Contribution to journalArticlepeer-review


    Dendritic cells (DCs) are the professional APCs of the immune system, enabling T cells to perceive and respond appropriately to potentially dangerous microbes, while also being able to maintain T cell tolerance toward self. In part, such tolerance can be determined by IL-10 released from certain types of regulatory T cells. IL-10 has previously been shown to render DCs unable to activate T cells and it has been assumed that this process represents a general block in maturation. Using serial analysis of gene expression, we show that IL-10 pretreatment of murine bone marrow-derived DCs alone causes significant changes in gene expression. Furthermore, these cells retain the ability to respond to Toll-like receptor agonists, but in a manner skewed toward the selective induction of mediators known to enhance local inflammation and innate immunity, among which we highlight a novel CXCR2 ligand, DC inflammatory protein-1. These data suggest that, while the presence of a protolerogenic and purportedly anti-inflammatory agent such as IL-10 precludes DCs from acquiring their potential as initiators of adaptive immunity, their ability to act as initiators of innate immunity in response to Toll-like receptor signaling is enhanced.
    Original languageEnglish
    Pages (from-to)2201-2209
    Number of pages8
    JournalJournal of Immunology
    Issue number4
    Publication statusPublished - 15 Feb 2004


    • Amino Acid Motifs
    • Animals
    • Bone Marrow Cells/immunology/metabolism
    • Cell Differentiation/genetics/immunology
    • Cell Line
    • Cell Line, Tumor
    • Cell Movement/genetics/*immunology
    • Cells, Cultured
    • Chemokines, CXC/antagonists & inhibitors/biosynthesis/genetics/physiology
    • Chemotaxis, Leukocyte/immunology
    • Dendritic Cells/cytology/*immunology/*metabolism
    • Gene Expression Regulation/*immunology
    • Gene Library
    • Humans
    • Immunity, Innate/genetics
    • Inflammation Mediators/*metabolism
    • Interleukin-10/*physiology
    • Lipopolysaccharides/pharmacology
    • Mice
    • Mice, Inbred BALB C
    • Mice, Inbred C57BL
    • Mice, Inbred CBA
    • Molecular Sequence Data
    • Monomeric GTP-Binding Proteins/antagonists &
    • inhibitors/*biosynthesis/*genetics/physiology
    • Neutrophil Infiltration/immunology
    • Nucleic Acid Amplification Techniques
    • RNA, Messenger/biosynthesis
    • Receptors, Interleukin-8B/physiology


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