Induction of Colonic Regulatory T Cells by Mesalamine by Activating the Aryl Hydrocarbon ReceptorSummary
Background & Aims: Mesalamine is a first-line drug for treatment of inflammatory bowel diseases (IBD). However, its mechanisms are not fully understood. CD4+ Foxp3+ regulatory T cells (Tregs) play a potential role in suppressing IBD. This study determined whether the anti-inflammatory activity o...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-07-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X17300735 |
| _version_ | 1819000315717877760 |
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| author | Kyoko Oh-oka Yuko Kojima Koichiro Uchida Kimiko Yoda Kayoko Ishimaru Shotaro Nakajima Jun Hemmi Hiroshi Kano Yoshiaki Fujii-Kuriyama Ryohei Katoh Hiroyuki Ito Atsuhito Nakao |
| author_facet | Kyoko Oh-oka Yuko Kojima Koichiro Uchida Kimiko Yoda Kayoko Ishimaru Shotaro Nakajima Jun Hemmi Hiroshi Kano Yoshiaki Fujii-Kuriyama Ryohei Katoh Hiroyuki Ito Atsuhito Nakao |
| author_sort | Kyoko Oh-oka |
| collection | DOAJ |
| description | Background & Aims: Mesalamine is a first-line drug for treatment of inflammatory bowel diseases (IBD). However, its mechanisms are not fully understood. CD4+ Foxp3+ regulatory T cells (Tregs) play a potential role in suppressing IBD. This study determined whether the anti-inflammatory activity of mesalamine is related to Treg induction in the colon. Methods: We examined the frequencies of Tregs in the colons of wild-type mice, mice deficient for aryl hydrocarbon receptor (AhR-/- mice), and bone marrowâchimeric mice lacking AhR in hematopoietic cells (BM-AhR-/- mice), following oral treatment with mesalamine. We also examined the effects of mesalamine on transforming growth factor (TGF)-β expression in the colon. Results: Treatment of wild-type mice with mesalamine increased the accumulation of Tregs in the colon and up-regulated the AhR target gene Cyp1A1, but this effect was not observed in AhR-/- or BM-AhR-/- mice. In addition, mesalamine promoted in vitro differentiation of naive T cells to Tregs, concomitant with AhR activation. Mice treated with mesalamine exhibited increased levels of the active form of TGF-β in the colon in an AhR-dependent manner and blockade of TGF-β signaling suppressed induction of Tregs by mesalamine in the colon. Furthermore, mice pretreated with mesalamine acquired resistance to dextran sodium sulfateâinduced colitis. Conclusions: We propose a novel anti-inflammatory mechanism of mesalamine for colitis: induction of Tregs in the colon via the AhR pathway, followed by TGF-β activation. Keywords: Mesalamine, Aryl Hydrocarbon Receptor, TGF-β, Regulatory T Cells |
| first_indexed | 2024-12-20T22:31:22Z |
| format | Article |
| id | doaj.art-fa32002dd88e4216a17dac4d9e5ca334 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-20T22:31:22Z |
| publishDate | 2017-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-fa32002dd88e4216a17dac4d9e5ca3342022-12-21T19:24:43ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2017-07-0141135151Induction of Colonic Regulatory T Cells by Mesalamine by Activating the Aryl Hydrocarbon ReceptorSummaryKyoko Oh-oka0Yuko Kojima1Koichiro Uchida2Kimiko Yoda3Kayoko Ishimaru4Shotaro Nakajima5Jun Hemmi6Hiroshi Kano7Yoshiaki Fujii-Kuriyama8Ryohei Katoh9Hiroyuki Ito10Atsuhito Nakao11Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, JapanThe Laboratory of Morphology and Image Analysis, Research Support Center, Juntendo University School of Medicine, Tokyo, JapanAtopy Research Center, Juntendo University School of Medicine, Tokyo, JapanDepartment of Pathology, Faculty of Medicine, University of Yamanashi, Yamanashi, JapanDepartment of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, JapanDepartment of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, JapanFood Science Research Laboratories, Division of Research and Development, Meiji Co, Ltd, Kanagawa, JapanFood Science Research Laboratories, Division of Research and Development, Meiji Co, Ltd, Kanagawa, JapanMedical Research Institute, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Pathology, Faculty of Medicine, University of Yamanashi, Yamanashi, JapanFood Science Research Laboratories, Division of Research and Development, Meiji Co, Ltd, Kanagawa, JapanDepartment of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan; Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan; Correspondence Address correspondence to: Atsuhito Nakao, MD, PhD, Department of Immunology, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi 409-3898, Japan. fax: 81-55-273-9542.Background & Aims: Mesalamine is a first-line drug for treatment of inflammatory bowel diseases (IBD). However, its mechanisms are not fully understood. CD4+ Foxp3+ regulatory T cells (Tregs) play a potential role in suppressing IBD. This study determined whether the anti-inflammatory activity of mesalamine is related to Treg induction in the colon. Methods: We examined the frequencies of Tregs in the colons of wild-type mice, mice deficient for aryl hydrocarbon receptor (AhR-/- mice), and bone marrowâchimeric mice lacking AhR in hematopoietic cells (BM-AhR-/- mice), following oral treatment with mesalamine. We also examined the effects of mesalamine on transforming growth factor (TGF)-β expression in the colon. Results: Treatment of wild-type mice with mesalamine increased the accumulation of Tregs in the colon and up-regulated the AhR target gene Cyp1A1, but this effect was not observed in AhR-/- or BM-AhR-/- mice. In addition, mesalamine promoted in vitro differentiation of naive T cells to Tregs, concomitant with AhR activation. Mice treated with mesalamine exhibited increased levels of the active form of TGF-β in the colon in an AhR-dependent manner and blockade of TGF-β signaling suppressed induction of Tregs by mesalamine in the colon. Furthermore, mice pretreated with mesalamine acquired resistance to dextran sodium sulfateâinduced colitis. Conclusions: We propose a novel anti-inflammatory mechanism of mesalamine for colitis: induction of Tregs in the colon via the AhR pathway, followed by TGF-β activation. Keywords: Mesalamine, Aryl Hydrocarbon Receptor, TGF-β, Regulatory T Cellshttp://www.sciencedirect.com/science/article/pii/S2352345X17300735 |
| spellingShingle | Kyoko Oh-oka Yuko Kojima Koichiro Uchida Kimiko Yoda Kayoko Ishimaru Shotaro Nakajima Jun Hemmi Hiroshi Kano Yoshiaki Fujii-Kuriyama Ryohei Katoh Hiroyuki Ito Atsuhito Nakao Induction of Colonic Regulatory T Cells by Mesalamine by Activating the Aryl Hydrocarbon ReceptorSummary Cellular and Molecular Gastroenterology and Hepatology |
| title | Induction of Colonic Regulatory T Cells by Mesalamine by Activating the Aryl Hydrocarbon ReceptorSummary |
| title_full | Induction of Colonic Regulatory T Cells by Mesalamine by Activating the Aryl Hydrocarbon ReceptorSummary |
| title_fullStr | Induction of Colonic Regulatory T Cells by Mesalamine by Activating the Aryl Hydrocarbon ReceptorSummary |
| title_full_unstemmed | Induction of Colonic Regulatory T Cells by Mesalamine by Activating the Aryl Hydrocarbon ReceptorSummary |
| title_short | Induction of Colonic Regulatory T Cells by Mesalamine by Activating the Aryl Hydrocarbon ReceptorSummary |
| title_sort | induction of colonic regulatory t cells by mesalamine by activating the aryl hydrocarbon receptorsummary |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X17300735 |
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