Abstract
IL-12p40 is induced in macrophages and dendritic cells (DC) after activation by microbial TLR ligands and cytokines and constitutes a component of IL-12 and IL-23. In an effort to understand the location and kinetics of these cytokines during the course of an immune response, we generated knockin (gene-targeted) mice that express the p40 gene linked via a viral internal ribosome entry site element with fluorescent reporters, eYFP or eGFP. Macrophages and DC from these mice faithfully reported biallelic p40 induction using the fluorescent marker. s.c. inoculation with Listeria monocytogenes or LPS led to a rapid, but transient, accumulation of p40-expressing DC in draining lymph nodes, which could be blocked by the addition of pertussis toxin. In situ analysis also revealed the accumulation of IL-12p40 protein around high endothelial venules located in close proximity to p40-expressing DC. Consistent with the in vivo findings, in vitro-activated DC that expressed p40 migrated to draining lymph nodes and promoted Th1 differentiation more efficiently than DC that did not express p40. Accordingly, these mice provide a valuable tool for tracking critical functions of DC in vivo and should bestow a useful reagent for exploring the effector biology of these cells in models of infectious disease, cancer immunity, and vaccine development.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Animals
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Bacterial Proteins / biosynthesis
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cell Movement / genetics
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Cell Movement / 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 Targeting
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Interleukin-12 / biosynthesis
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Interleukin-12 / deficiency
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Interleukin-12 / genetics
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Interleukin-12 / physiology*
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Interleukin-12 Subunit p40
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Interleukin-23
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Interleukin-23 Subunit p19
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Interleukins / biosynthesis
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Interleukins / genetics
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Interleukins / physiology*
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Ligands
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Luminescent Proteins / biosynthesis
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Lymph Nodes / microbiology
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Macrophages, Peritoneal / immunology
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Macrophages, Peritoneal / metabolism
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Male
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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, Knockout
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Mice, Mutant Strains
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Mice, Transgenic
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Protein Subunits / biosynthesis
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Protein Subunits / deficiency
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Protein Subunits / genetics
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Protein Subunits / physiology*
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Th1 Cells / cytology*
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Th1 Cells / immunology
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Toll-Like Receptors / metabolism
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Toll-Like Receptors / physiology
Substances
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Bacterial Proteins
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Il23a protein, mouse
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Interleukin-12 Subunit p40
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Interleukin-23
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Interleukin-23 Subunit p19
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Interleukins
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Ligands
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Luminescent Proteins
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Protein Subunits
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Toll-Like Receptors
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yellow fluorescent protein, Bacteria
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Interleukin-12