Abstract
Psoriasis is a chronic inflammatory skin disease in which Th17 cells play a crucial role. Since indigenous gut microbiota influences the development and reactivity of immune cells, we analyzed the link among microbiota, T cells and the formation of psoriatic lesions in the imiquimod-induced murine model of psoriasis. To explore the role of microbiota, we induced skin inflammation in germ-free (GF), broad-spectrum antibiotic (ATB)-treated or conventional (CV) BALB/c and C57BL/6 mice. We found that both mice reared in GF conditions for several generations and CV mice treated with ATB were more resistant to imiquimod-induced skin inflammation than CV mice. The ATB treatment dramatically changed the diversity of gut bacteria, which remained stable after subsequent imiquimod application; ATB treatment resulted in a substantial increase in the order Lactobacillales and a significant decrease in Coriobacteriales and Clostridiales. Moreover, as compared to CV mice, imiquimod induced a lower degree of local and systemic Th17 activation in both GF and ATB-treated mice. These findings suggest that gut microbiota control imiquimod-induced skin inflammation by altering the T cell response.
MeSH terms
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Actinobacteria / drug effects
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Actinobacteria / physiology
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Aminoquinolines / pharmacology
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Animals
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Anti-Bacterial Agents / pharmacology
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Clostridiales / drug effects
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Clostridiales / physiology
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Disease Models, Animal
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Female
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Gastrointestinal Microbiome / drug effects
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Gastrointestinal Microbiome / physiology*
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Gene Expression
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Germ-Free Life
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Humans
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Imiquimod
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Interleukin-17 / genetics
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Interleukin-17 / immunology
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Lactobacillales / drug effects
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Lactobacillales / physiology
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Lymphocyte Activation / drug effects
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
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Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
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Psoriasis / chemically induced
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Psoriasis / immunology*
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Psoriasis / microbiology*
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Psoriasis / pathology
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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Receptors, Antigen, T-Cell, gamma-delta / immunology
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Skin / drug effects
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Skin / immunology*
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Skin / microbiology
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Skin / pathology
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Species Specificity
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Th17 Cells / drug effects
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Th17 Cells / immunology*
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Th17 Cells / microbiology
Substances
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Aminoquinolines
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Anti-Bacterial Agents
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Interleukin-17
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Antigen, T-Cell, gamma-delta
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Rorc protein, mouse
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Imiquimod
Grants and funding
This work was supported by Ministry of Health of the Czech Republic (15-30782A;
http://www.azvcr.cz/; JH), by Czech Science Foundation (P303/12/0535;
https://gacr.cz/; MKv), by Institutional Research Concept (RVO: 61388971) and by European Regional Development Fund BIOCEV (CZ.1.05/1.1.00/02.0109;
www.biocev.eu; MKo). All rights reserved. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.