Homeostasis of biliary and intestinal systems dependent on microbiota regulated by SP-D
Project/Area Number |
18K07166
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 49070:Immunology-related
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Research Institution | Toho University (2019-2021) The University of Tokyo (2018) |
Principal Investigator |
Nishio Junko 東邦大学, 医学部, 准教授(寄付講座) (40598679)
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | サーファクタントプロテインD / Lactobacillus murinus / ディスバイオーシス / IL-22 / 硬化性胆管炎 / サーファクタントプロテインC / 抗菌ペプチド / 胆管上皮細胞 / iNOS / SP-D / 原発性硬化性胆管炎 / 線維化 / 炎症性腸疾患 / 胆嚢 / 腸内細菌叢 |
Outline of Final Research Achievements |
Surfactant protein D (SP-D) produced in the gall bladder (GB) regulated gut microbiota by its anti-microbial activity against a group of bacteria including Lactobacillus murinus. In SP-D-deficient mice which has dysbiosis in the gut, IL-22-producing cells such as gdT and NKp46 cells and CD4+ lymphoid tissue-inducers were decreased, leading to high sensitivity to colitis. In sclerosing cholangitis model mice in which SP-D was genetically depleted, the diseases was not affected. However, it is worthy of addressing the effects of SP-D on other GB or bile duct diseases including cancer and infection.
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Academic Significance and Societal Importance of the Research Achievements |
SP-Dは、肺胞上皮細胞から分泌される抗菌ペプチドとして肺感染防御機構に貢献していることが知られていたが、本研究により、SP-Dが肺以外にも胆嚢から産生され、腸内細菌を制御し、腸管粘膜のIL-22産生細胞の維持を介して腸管恒常性に貢献している可能性があるという新しい概念を生んだ。線維性胆管炎に対してSP-D欠損による腸内ディスバイオーシスの影響は認めなかったが、感染症やがんなどの他の胆のう疾患に対する影響を検討する価値は十分にある。何らかの影響が認められれば、炎症性腸疾患のみならず、胆嚢疾患に関してSP-Dを標的とした治療基盤を創出する可能性を持つ。
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Report
(5 results)
Research Products
(12 results)
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[Journal Article] Identification of U11snRNA as an endogenous agonist of TLR7-mediated immune pathogenesis.2019
Author(s)
Negishi H, Endo N, Nakajima Y, Nishiyama T, Tabunoki Y, Nishio J, Koshiba R, Matsuda A, Matsuki K, Okamura T, Negishi-Koga T, Ichinohe T, Takemura S, Ishiwata H, Iemura SI, Natsume T, Abe T, Kiyonari H, Doi T, Hangai S, Yanai H, Fujio K, Yamamoto K, Taniguchi T.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 116
Issue: 47
Pages: 23653-23661
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] The effect of anti‐CX3CL1 monoclonal antibody treatment in arthritis and interstitial lung disease of SKG mice.2019
Author(s)
Satoshi Mizutani, Kanoh Kondo, Syotaro Masuoka, Soichi Yamada, Sei Muraoka, Natsuko Kusunoki, Naoto Ishii, Yoshikazu Kuboi, Toshio Imai, Junko Nishio, Toshihiro Nanki
Organizer
Keystone symposia; FIbrosis and Tissue Repair:From Molecules and Mechanics to Therapeutic Approaches
Related Report
Int'l Joint Research