Toll-Like Receptor 7 Agonist–Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells

Hiroki Kiyohara, Tomohisa Sujino, Toshiaki Teratani, Kentaro Miyamoto, Mari Mochizuki Arai, Ena Nomura, Yosuke Harada, Ryo Aoki, Yuzo Koda, Yohei Mikami, Shinta Mizuno, Makoto Naganuma, Tadakazu Hisamatsu, Takanori Kanai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background & Aims: Psoriasis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases occurring in the skin and gut, respectively. It is well established that psoriasis and IBD have high concordance rates, and similar changes in immune cells and microbiome composition have been reported in both conditions. To study this connection, we used a combination murine model of psoriatic dermatitis and colitis in which mice were treated topically with the Toll-like receptor 7 agonist imiquimod (IMQ) and fed dextran sulfate sodium (DSS). Methods: We applied IMQ topically to B6 mice (IMQ mice) and subsequently fed them 2% DSS in their drinking water. Disease activity and immune cell phenotypes were analyzed, and the microbial composition of fecal samples was investigated using 16S ribosomal RNA sequencing. We transplanted feces from IMQ mice to germ-free IQI/Jic (IQI) mice and fed them DSS to assess the effect of the gut microbiome on disease. Results: We first confirmed that IMQ mice showed accelerated DSS colitis. IMQ mice had decreased numbers of IgD+ and IgM+ B cells and increased numbers of non–cytokine-producing macrophages in the gut. Moreover, the gut microbiomes of IMQ mice were perturbed, with significant reductions of Lactobacillus johnsonii and Lactobacillus reuteri populations. Germ-free mice transplanted with feces from IMQ mice, but not with feces from untreated mice, also developed exacerbated DSS colitis. Conclusions: These results suggest that skin inflammation may contribute to pathogenic conditions in the gut via immunologic and microbiological changes. Our finding of a novel potential skin–gut interaction provides new insights into the coincidence of psoriasis and IBD.

Original languageEnglish
Pages (from-to)135-156
Number of pages22
JournalCMGH
Volume7
Issue number1
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Toll-Like Receptor 7
imiquimod
Dextran Sulfate
Dermatitis
Colitis
Inflammatory Bowel Diseases
Psoriasis
Feces
Gastrointestinal Microbiome
Lactobacillus reuteri
16S Ribosomal RNA
RNA Sequence Analysis
Immunoglobulin D
Skin
Microbiota
Immune System Diseases
Drinking Water
Immunoglobulin M

Keywords

  • Dermatitis
  • Gut Microbiome
  • Inflammatory Bowel Disease

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Toll-Like Receptor 7 Agonist–Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells. / Kiyohara, Hiroki; Sujino, Tomohisa; Teratani, Toshiaki; Miyamoto, Kentaro; Arai, Mari Mochizuki; Nomura, Ena; Harada, Yosuke; Aoki, Ryo; Koda, Yuzo; Mikami, Yohei; Mizuno, Shinta; Naganuma, Makoto; Hisamatsu, Tadakazu; Kanai, Takanori.

In: CMGH, Vol. 7, No. 1, 01.01.2019, p. 135-156.

Research output: Contribution to journalArticle

Kiyohara, H, Sujino, T, Teratani, T, Miyamoto, K, Arai, MM, Nomura, E, Harada, Y, Aoki, R, Koda, Y, Mikami, Y, Mizuno, S, Naganuma, M, Hisamatsu, T & Kanai, T 2019, 'Toll-Like Receptor 7 Agonist–Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells', CMGH, vol. 7, no. 1, pp. 135-156. https://doi.org/10.1016/j.jcmgh.2018.09.010
Kiyohara, Hiroki ; Sujino, Tomohisa ; Teratani, Toshiaki ; Miyamoto, Kentaro ; Arai, Mari Mochizuki ; Nomura, Ena ; Harada, Yosuke ; Aoki, Ryo ; Koda, Yuzo ; Mikami, Yohei ; Mizuno, Shinta ; Naganuma, Makoto ; Hisamatsu, Tadakazu ; Kanai, Takanori. / Toll-Like Receptor 7 Agonist–Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells. In: CMGH. 2019 ; Vol. 7, No. 1. pp. 135-156.
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abstract = "Background & Aims: Psoriasis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases occurring in the skin and gut, respectively. It is well established that psoriasis and IBD have high concordance rates, and similar changes in immune cells and microbiome composition have been reported in both conditions. To study this connection, we used a combination murine model of psoriatic dermatitis and colitis in which mice were treated topically with the Toll-like receptor 7 agonist imiquimod (IMQ) and fed dextran sulfate sodium (DSS). Methods: We applied IMQ topically to B6 mice (IMQ mice) and subsequently fed them 2{\%} DSS in their drinking water. Disease activity and immune cell phenotypes were analyzed, and the microbial composition of fecal samples was investigated using 16S ribosomal RNA sequencing. We transplanted feces from IMQ mice to germ-free IQI/Jic (IQI) mice and fed them DSS to assess the effect of the gut microbiome on disease. Results: We first confirmed that IMQ mice showed accelerated DSS colitis. IMQ mice had decreased numbers of IgD+ and IgM+ B cells and increased numbers of non–cytokine-producing macrophages in the gut. Moreover, the gut microbiomes of IMQ mice were perturbed, with significant reductions of Lactobacillus johnsonii and Lactobacillus reuteri populations. Germ-free mice transplanted with feces from IMQ mice, but not with feces from untreated mice, also developed exacerbated DSS colitis. Conclusions: These results suggest that skin inflammation may contribute to pathogenic conditions in the gut via immunologic and microbiological changes. Our finding of a novel potential skin–gut interaction provides new insights into the coincidence of psoriasis and IBD.",
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AU - Sujino, Tomohisa

AU - Teratani, Toshiaki

AU - Miyamoto, Kentaro

AU - Arai, Mari Mochizuki

AU - Nomura, Ena

AU - Harada, Yosuke

AU - Aoki, Ryo

AU - Koda, Yuzo

AU - Mikami, Yohei

AU - Mizuno, Shinta

AU - Naganuma, Makoto

AU - Hisamatsu, Tadakazu

AU - Kanai, Takanori

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N2 - Background & Aims: Psoriasis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases occurring in the skin and gut, respectively. It is well established that psoriasis and IBD have high concordance rates, and similar changes in immune cells and microbiome composition have been reported in both conditions. To study this connection, we used a combination murine model of psoriatic dermatitis and colitis in which mice were treated topically with the Toll-like receptor 7 agonist imiquimod (IMQ) and fed dextran sulfate sodium (DSS). Methods: We applied IMQ topically to B6 mice (IMQ mice) and subsequently fed them 2% DSS in their drinking water. Disease activity and immune cell phenotypes were analyzed, and the microbial composition of fecal samples was investigated using 16S ribosomal RNA sequencing. We transplanted feces from IMQ mice to germ-free IQI/Jic (IQI) mice and fed them DSS to assess the effect of the gut microbiome on disease. Results: We first confirmed that IMQ mice showed accelerated DSS colitis. IMQ mice had decreased numbers of IgD+ and IgM+ B cells and increased numbers of non–cytokine-producing macrophages in the gut. Moreover, the gut microbiomes of IMQ mice were perturbed, with significant reductions of Lactobacillus johnsonii and Lactobacillus reuteri populations. Germ-free mice transplanted with feces from IMQ mice, but not with feces from untreated mice, also developed exacerbated DSS colitis. Conclusions: These results suggest that skin inflammation may contribute to pathogenic conditions in the gut via immunologic and microbiological changes. Our finding of a novel potential skin–gut interaction provides new insights into the coincidence of psoriasis and IBD.

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