Abstract
IL-7 is a major regulator of lymphocyte homeostasis; however, little is known about the mechanisms that regulate IL-7 production. To study Il7 gene regulation in vivo, we generated a novel IL-7-reporter mouse, which allows the non-invasive quantification of Il7 gene activity in live mice and, additionally, the simultaneous activation/inactivation of target genes in IL-7-producing cells. With these IL-7-reporter mice, we identify thymus, skin and intestine as major sources of IL-7 in vivo. Importantly, we show that IFN-gamma and the commensal microflora promote steady-state IL-7 production in the intestine. Furthermore, we demonstrate that the blockade of IFN-gamma signaling in intestinal epithelial cells strongly reduces their IFN-gamma-driven IL-7 production. In summary, our data suggest a feedback loop in which commensal bacteria drive IFN-gamma production by lymphocytes, which in turn promotes epithelial cell IL-7 production and the survival of IL-7-dependent lymphocytes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Bacterial Agents / administration & dosage
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Cell Line, Tumor
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Cell Survival / drug effects
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Cell Survival / genetics
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Cell Survival / immunology
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Chromosomes, Artificial, Bacterial
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Dexamethasone / pharmacology
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Feedback, Physiological
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / immunology
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Interferon-gamma / genetics
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Interferon-gamma / immunology
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Interferon-gamma / metabolism*
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Interleukin-7 / genetics
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Interleukin-7 / immunology
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Interleukin-7 / metabolism*
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Intestinal Mucosa / drug effects
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Intestinal Mucosa / immunology
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Intestinal Mucosa / metabolism*
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Intestinal Mucosa / pathology
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Intestines / drug effects
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Intestines / microbiology
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Intestines / pathology
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Metagenome / drug effects
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Metagenome / immunology
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Mice
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Mice, Transgenic
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Signal Transduction / drug effects
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Signal Transduction / genetics
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
Substances
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Anti-Bacterial Agents
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Interleukin-7
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Luminescent Proteins
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Dexamethasone
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Interferon-gamma