Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Animals
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Line
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Cell Line, Tumor
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Cell Movement / genetics
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Cell Movement / immunology*
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Cells, Cultured
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Chemokines, CXC / antagonists & inhibitors
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Chemokines, CXC / biosynthesis
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Chemokines, CXC / genetics
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Chemokines, CXC / physiology
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Chemotaxis, Leukocyte / immunology
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Gene Expression Regulation / immunology*
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Gene Library
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Humans
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Immunity, Innate / genetics
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Inflammation Mediators / metabolism*
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Interleukin-10 / physiology*
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Lipopolysaccharides / pharmacology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Molecular Sequence Data
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Monomeric GTP-Binding Proteins / antagonists & inhibitors
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Monomeric GTP-Binding Proteins / biosynthesis*
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Monomeric GTP-Binding Proteins / genetics*
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Monomeric GTP-Binding Proteins / physiology
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Neutrophil Infiltration / immunology
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Nucleic Acid Amplification Techniques
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RNA, Messenger / biosynthesis
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Receptors, Interleukin-8B / physiology
Substances
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Chemokines, CXC
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Inflammation Mediators
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Lipopolysaccharides
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RNA, Messenger
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Receptors, Interleukin-8B
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Tgtp protein, mouse
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Interleukin-10
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Monomeric GTP-Binding Proteins
Associated data
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GENBANK/AY311403
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GENBANK/AY311405
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RefSeq/XM_284097