Ahr欠損マウスにおける炎症性腸疾患と網羅的エピゲノム解析

大迫 誠一郎; 鈴木 壮登; 矢田 健太郎; 上羽 悟史; 陳 旻岑; 荻原 春; 松島 綱治; 市原 学

doi:10.14869/toxpt.47.1.0_O-11

The 47th Annual Meeting of the Japanese Society of Toxicology

Session ID : O-11

DOI https://doi.org/10.14869/toxpt.47.1.0_O-11

Conference information

Host: The Japanese Society of Toxicology

Name : The 47th Annual Meeting of the Japanese Society of Toxicology

Date : 2020 -

Oral

Inflammatory bowel disease observed in the Ahr-null mice with an analysis of epigenome in genome-wide

*Seiichiroh OHSAKO, Soto SUZUKI, Kentaro YADA, Satoshi UEHA, Ming-Chen CHEN, Haru OGIWARA, Kouji MATSUSHIMA, Gaku ICHIHARA

Author information

*Seiichiroh OHSAKO
Laboratory of Environmental Health Sciences, Graduate School of Medicine, The University of Tokyo
Soto SUZUKI
Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science
Kentaro YADA
Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science
Satoshi UEHA
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science
Ming-Chen CHEN
Laboratory of Environmental Health Sciences, Graduate School of Medicine, The University of Tokyo
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science
Haru OGIWARA
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science
Kouji MATSUSHIMA
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science
Gaku ICHIHARA
Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science

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Abstract

Rectal prolapse, thickened colon, enlargement of the spleen and mesenteric lymph nodes were observed in all AhrKO mice. Flow cytometry revealed that Th17 cells significantly increased in the spleen and colonic lamina propria, whereas no obvious differences in Treg cells. Importantly, metagenome analysis with feces of colon revealed a facility-specific flora. RRBS using liver DNA showed hypomethylation in the ARNTL/BMAL1 gene. Our finding indicates that Ahr dysfunction is involved in IBD pathogenesis with changes probably in the gut flora producing Ahr-endogenous ligands.

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