Development of prophylactic strategies for acute and chronic radiation-induced gastrointestinal syndrome by targeting the innate immune system
| Project/Area Number |
16K19148
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Osaka University (2018-2019)
Chiba University (2016-2017) |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 放射線性消化管症候群 / 自然免疫 / 放射線誘導性腸線維症 / 好酸球 / 放射線誘導性口腔内粘膜炎 / TLR3 / 放射線誘導性小腸線維症 / 筋繊維芽細胞 / 放射線 / 小腸線維症 / 口腔内粘膜炎 |
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| Outline of Final Research Achievements |
Gastrointestinal syndrome is the most troublesome side effect of radiation therapy that occurs during the acute and chronic phases if the gastrointestinal tract is exposed to high doses of radiation for cancer treatment. In this project, we investigated the role of innate immunity in the pathogenesis of gastrointestinal syndrome. Consequentially, we elucidated the disease mechanisms of radiation-induced intestinal fibrosis (RIF), in which eosinophils play a critical role in activation of intestinal myofibroblasts to promote fibrogenesis, and proposed eosinophil-depleting agents as an effective prophylactic measure for the management of RIF. In addition, we also found that epithelial damage via the activation of Toll-like receptor 3 (TLR3) post-irradiation is a critical event for ulcer formation and subsequent leukocyte infiltration in radiation-induced oral mucositis (RIOM), and suggested TLR3 inhibitors as a potential preventive measure against RIOM.
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| Academic Significance and Societal Importance of the Research Achievements |
放射線性消化管症候群のうち、腸線維症と口腔内粘膜炎はいずれも病態成立過程が十分に明らかとなっていないため、対症療法以外に手立てがなく、癌患者の生活の質を大きく低下させる問題となっている。本研究により、それぞれの疾患の病態成立過程において好酸球やTLR3を中心とした自然免疫機構が重要な役割を果たすことが明らかとなったことで、当該機構を標的とした新たな予防・治療戦略の開発が進むと期待される。また、同様の対処法は、耐容線量の増加や放射線治療期間の延長によって放射線療法のがん治療効果を向上させるという目的のためにも応用されることが期待される。
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Report
(5 results)
Research Products
(42 results)
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[Journal Article] Generation of tumor antigen-specific murine CD8+ T cells with enhanced anti-tumor activity via highly efficient CRISPR/Cas9 genome editing2018
Author(s)
Ouchi Y, Patil A, Tamura Y, Nishimasu H, Negishi A, Paul SK, Takemura N, Satoh T, Kimura Y, Kurachi M, Nureki O, Nakai K, Kiyono H, Uematsu S.
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Journal Title
International Immunology
Volume: 30
Issue: 4
Pages: 141-154
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception.2018
Author(s)
Maruyama K, Takayama Y, Sugisawa E, Yamanoi Y, Yokawa T, Kondo T, Ishibashi KI, Sahoo BR, Takemura N, Mori Y, Kanemaru H, Kumagai Y, Martino MM, Yoshioka Y, Nishijo H, Tanaka H, Sasaki A, Ohno N, Iwakura Y, Moriyama Y, Nomura M, Akira S, Tominaga M.
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Journal Title
iScience
Volume: 6
Pages: 306-318
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Eosinophil depletion suppresses radiation-induced small intestinal fibrosis.2018
Author(s)
Takemura N, Kurashima Y, Mori Y, Okada K, Ogino T, Osawa H, Matsuno H, Aayam L, Kaneto S, Park EJ, Sato S, Matsunaga K, Tamura Y, Ouchi Y, Kumagai Y, Kobayashi D, Suzuki Y, Yoshioka Y, Nishimura J, Mori M, Ishii KJ, Rothenberg ME, Kiyono H, Akira S, Uematsu S.
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Journal Title
Sci Transl Med.
Volume: --
Issue: 429
Pages: 264-273
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A Refined Culture System for Human Induced Pluripotent Stem Cell-Derived Intestinal Epithelial Organoids.2017
Author(s)
Takahashi Y, Sato S, Kurashima Y, Yamamoto T, Kurokawa S, Yuki Y, Takemura N, Uematsu S, Lai CY, Otsu M, Matsuno H, Osawa H, Mizushima T, Nishimura J, Hayashi M, Yamaguchi T, Kiyono H.
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Journal Title
Stem Cell Reports.
Volume: --
Issue: 1
Pages: 314-328
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Herpes simplex virus-1 evasion of CD8+ T cell accumulation contributes to viral encephalitis.2017
Author(s)
Koyanagi N, Imai T, Shindo K, Sato A, Fujii W, Ichinohe T, Takemura N, Kakuta S, Uematsu S, Kiyono H, Maruzuru Y, Arii J, Kato A, Kawaguchi Y.
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Journal Title
J Clin Invest.
Volume: 127
Issue: 10
Pages: 3784-3795
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Bone-protective Functions of Netrin 1 Protein2016
Author(s)
Kenta Maruyama, Takahiko Kawasaki, Masahide Hamaguchi, Motomu Hashimoto, Moritoshi Furu, Hiromu Ito, Takao Fujii, Naoki Takemura, Thangaraj Karuppuchamy, Takeshi Kondo, Takumi Kawasaki, Masahiro Fukusaka, Takuma Misawa, Tatsuya Saitoh, Yutaka Suzuki, Mikael M Martino, Yutaro Kumagai, and Shizuo Akira
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Journal Title
Journal of Biological Chemistry
Volume: 291
Issue: 46
Pages: 23854-23868
DOI
Related Report
Peer Reviewed
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[Journal Article] Fine Particles Induce Alveolar Macrophage Death and Interleukin-1α Release to Promote Inducible Bronchus-Associated Lymphoid Tissue Formation.2016
Author(s)
Kuroda E, Ozasa K, Temizoz B, Ohata K, Koo CX, Kanuma T, Kusakabe T, Kobari S, Horie M, Morimoto Y, Nakajima S, Kabashima K, Ziegler SF, Iwakura Y, Ise W, Kurosaki T, Nagatake T, Kunisawa J, Takemura N, Uematsu S, Hayashi M, Aoshi T, Kobiyama K, Coban C, Ishii KJ.
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Journal Title
Immunity.
Volume: 45(6)
Issue: 6
Pages: 1299-1310
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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