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Establishment of transplantation tolerance induction by controlling inflammation

Research Project

Project/Area Number 18K08558
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Fujino Masayuki  国立感染症研究所, エイズ研究センター, 客員研究員 (50392329)

Co-Investigator(Kenkyū-buntansha) 森 一泰  国立感染症研究所, エイズ研究センター, 主任研究官 (20270655)
梨井 康  国立研究開発法人国立成育医療研究センター, 移植免疫研究室, 室長 (60321890)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords炎症 / 防御免疫 / 免疫 / 移植免疫
Outline of Final Research Achievements

This study is based on the concept that the regulation of inflammation induces suppressive type of acquired immunity. In this study, we analyzed the mechanism by which infection with glycan-mutated AIDS viruses suppresses excessive immune response, and the mechanism of infection control by different subtypes of AIDS viruses induced by live vaccines in ex-vivo models. In addition, the effects of hydrogenated water, natural herb-derived ingredients, and amino acids on inflammation and immune regulation were clarified using various animal models of disease (inflammatory disease model, autoimmune disease model, and organ transplantation model).

Academic Significance and Societal Importance of the Research Achievements

日本で生体肝移植が開始され30年以上経過しているが、移植後の拒絶反応抑制のために、臓器移植患者は終生の免疫抑制剤投与が必要とされる。一方、長期に渡る免疫抑制剤の投与は、感染症ならびに癌の発生頻度を上昇させる。そのために、免疫抑制剤の投与量の減量あるいは離脱方法が検討されているが、安全に減量あるいは離脱可能な方法は未だ開発されていない。本研究の成果は、炎症の制御が移植免疫寛容誘導の確立に寄与するのとの仮説を証明するものであり、今後移植免疫寛容の誘導につながる炎症制御方法を見出すことにより、長期安定的な移植免疫寛容の誘導確立に繋がることが期待される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (35 results)

All 2021 2020 2019 2018

All Journal Article (27 results) (of which Int'l Joint Research: 18 results,  Peer Reviewed: 26 results,  Open Access: 13 results) Presentation (8 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] The effects of oral administration of Aureobasidium pullulans-cultured fluid containing β-glucan on concanavalin A injected mice2021

    • Author(s)
      Wang Zhidan、Ma Kuai、Fujino Masayuki、Kusano Kisato、Yi Shuang-Qin、Iwai Atsushi、Li Xiao-Kang
    • Journal Title

      Heliyon

      Volume: 7 Issue: 6 Pages: e07277-e07277

    • DOI

      10.1016/j.heliyon.2021.e07277

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Mesenchymal‐Epithelial Transition Factor‐Agonistic Antibody Accelerates Cirrhotic Liver Regeneration and Improves Mouse Survival Following Partial Hepatectomy2021

    • Author(s)
      Ma Kuai、Que Weitao、Hu Xin、Guo Wen‐Zhi、Gu Er‐li、Zhong Liang、Morello Virginia、Cazzanti Manuela、Michieli Paolo、Takahara Terumi、Li Xiao‐Kang
    • Journal Title

      Liver Transplantation

      Volume: 28 Issue: 5 Pages: 782-793

    • DOI

      10.1002/lt.26301

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] β-glucan from Aureobasidium pullulans augments the anti-tumor immune responses through activated tumor-associated dendritic cells2021

    • Author(s)
      Shui Yifang、Hu Xin、Hirano Hiroshi、Kusano Kisato、Tsukamoto Hirotake、Li Mengquan、Hasumi Kenichiro、Guo Wen-Zhi、Li Xiao-Kang
    • Journal Title

      International Immunopharmacology

      Volume: 101 Pages: 108265-108265

    • DOI

      10.1016/j.intimp.2021.108265

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Oridonin Prolongs the Survival of Mouse Cardiac Allografts by Attenuating the NF-κB/NLRP3 Pathway2021

    • Author(s)
      Du Xiaoxiao、Que Weitao、Hu Xin、Yu Xiao、Guo Wen-Zhi、Zhang Shuijun、Li Xiao-Kang
    • Journal Title

      Frontiers in Immunology

      Volume: 12 Pages: 719574-719574

    • DOI

      10.3389/fimmu.2021.719574

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 5‐Aminolevulinic acid/sodium ferrous citrate enhanced the antitumor effects of programmed cell death‐ligand 1 blockade by regulation of exhausted T cell metabolism in a melanoma model2021

    • Author(s)
      Hu Xin、Que Weitao、Hirano Hiroshi、Wang Zhidan、Nozawa Naoko、Ishii Takuya、Ishizuka Masahiro、Ito Hidenori、Takahashi Kiwamu、Nakajima Motowo、Tanaka Tohru、Zhu Ping、Guo Wen‐Zhi、Li Xiao‐Kang
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 7 Pages: 2652-2663

    • DOI

      10.1111/cas.14930

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 5-aminolevulinic acid combined with sodium ferrous citrate ameliorated lupus nephritis in a mouse chronic graft-versus-host disease model2021

    • Author(s)
      Liu Chi、Wang Zhidan、Hu Xin、Ito Hidenori、Takahashi Kiwamu、Nakajima Motowo、Tanaka Tohru、Zhu Ping、Li Xiao-Kang
    • Journal Title

      International Immunopharmacology

      Volume: 96 Pages: 107626-107626

    • DOI

      10.1016/j.intimp.2021.107626

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Small-Molecule Anti-HIV-1 Agents Based on HIV-1 Capsid Proteins2021

    • Author(s)
      Kobayakawa Takuya、Yokoyama Masaru、Tsuji Kohei、Fujino Masayuki、Kurakami Masaki、Boku Sayaka、Nakayama Miyuki、Kaneko Moemi、Ohashi Nami、Kotani Osamu、Murakami Tsutomu、Sato Hironori、Tamamura Hirokazu
    • Journal Title

      Biomolecules

      Volume: 11 Issue: 2 Pages: 208-208

    • DOI

      10.3390/biom11020208

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potent leads based on CA-19L, an anti-HIV active HIV-1 capsid fragment2021

    • Author(s)
      Tsuji Kohei、Wang Rongyi、Kobayakawa Takuya、Owusu Kofi Baffour-Awuah、Fujino Masayuki、Kaneko Moemi、Yamamoto Naoki、Murakami Tsutomu、Tamamura Hirokazu
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 30 Pages: 115923-115923

    • DOI

      10.1016/j.bmc.2020.115923

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Monotherapy With Anti-CD70 Antibody Causes Long-Term Mouse Cardiac Allograft Acceptance With Induction of Tolerogenic Dendritic Cells2021

    • Author(s)
      Zhao Jing、Que Weitao、Du Xiaoxiao、Fujino Masayuki、Ichimaru Naotsugu、Ueta Hisashi、Tokuda Nobuko、Guo Wen-zhi、Zabrocki Piotr、de Haard Hans、Nonomura Norio、Li Xiao-Kang
    • Journal Title

      Frontiers in Immunology

      Volume: 11 Pages: 555996-555996

    • DOI

      10.3389/fimmu.2020.555996

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hydrogen-rich water protects against liver injury in nonalcoholic steatohepatitis through HO-1 enhancement via IL-10 and Sirt 1 signaling2021

    • Author(s)
      Li Shao-Wei、Takahara Terumi、Que Weitao、Fujino Masayuki、Guo Wen-Zhi、Hirano Shin-Ichi、Ye Li-Ping、Li Xiao-Kang
    • Journal Title

      American Journal of Physiology-Gastrointestinal and Liver Physiology

      Volume: 320 Issue: 4 Pages: G450-G463

    • DOI

      10.1152/ajpgi.00158.2020

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Protective Immune Responses Elicited by Deglycosylated Live-Attenuated Simian Immunodeficiency Virus Vaccine Are Associated with IL-15 Effector Functions2020

    • Author(s)
      Watanabe Satoru、Fujino Masayuki、Saito Yohei、Ahmed Nursarat、Sato Hirotaka、Sugimoto Chie、Okamura Tomotaka、Hanaki Kenichi、Nakayama Emi E.、Shioda Tatsuo、Matsushima Kouji、Ansari Aftab A.、Villinger Francois、Mori Kazuyasu
    • Journal Title

      The Journal of Immunology

      Volume: 205 Issue: 5 Pages: 1331-1344

    • DOI

      10.4049/jimmunol.1901431

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bivalent HIV-1 fusion inhibitors based on peptidomimetics2020

    • Author(s)
      Kobayakawa Takuya、Ebihara Kento、Tsuji Kohei、Kawada Takuma、Fujino Masayuki、Honda Yuzuna、Ohashi Nami、Murakami Tsutomu、Tamamura Hirokazu
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 28 Issue: 24 Pages: 115812-115812

    • DOI

      10.1016/j.bmc.2020.115812

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Exploratory studies on CA-15L, an anti-HIV active HIV-1 capsid fragment2020

    • Author(s)
      Tsuji Kohei、Owusu Kofi Baffour-Awuah、Kobayakawa Takuya、Wang Rongyi、Fujino Masayuki、Kaneko Moemi、Yamamoto Naoki、Murakami Tsutomu、Tamamura Hirokazu
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 28 Issue: 11 Pages: 115488-115488

    • DOI

      10.1016/j.bmc.2020.115488

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hydrogen Gas Attenuates Hypoxic-Ischemic Brain Injury via Regulation of the MAPK/HO-1/PGC-1a Pathway in Neonatal Rats2020

    • Author(s)
      Wang Peipei、Zhao Mingyi、Chen Zhiheng、Wu Guojiao、Fujino Masayuki、Zhang Chen、Zhou Wenjuan、Zhao Mengwen、Hirano Shin-ichi、Li Xiao-Kang、Zhao Lingling
    • Journal Title

      Oxidative Medicine and Cellular Longevity

      Volume: 2020 Pages: 1-16

    • DOI

      10.1155/2020/6978784

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunomodulatory effects of Salvianolic acid B in a spontaneous abortion mouse model2020

    • Author(s)
      Wang Jing、Liu Chi、Que Weitao、Fujino Masayuki、Tong Guoqing、Yan Hua、Li Xiao-Kang
    • Journal Title

      Journal of Reproductive Immunology

      Volume: 137 Pages: 103075-103075

    • DOI

      10.1016/j.jri.2019.103075

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prolonged cold ischemia time in mouse heart transplantation using supercooling preservation2019

    • Author(s)
      4.Que W, Hu X, Fujino M, Terayama H, Sakabe K, Fukunishi N, Zhu P, Yi SQ, Yamada Y, Zhong L, Li XK
    • Journal Title

      Transplantation

      Volume: 00 Issue: 9 Pages: 00-00

    • DOI

      10.1097/tp.0000000000003089

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Novel Molecular Targets Participating in Myocardial Ischemia-Reperfusion Injury and Cardioprotection2019

    • Author(s)
      Liu Nan-Bo、Wu Min、Chen Chen、Fujino Masayuki、Huang Jing-Song、Zhu Ping、Li Xiao-Kang
    • Journal Title

      Cardiology Research and Practice

      Volume: 2019 Pages: 1-16

    • DOI

      10.1155/2019/6935147

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 5‐ALA/SFC enhances HO‐1 expression through the MAPK/Nrf2 antioxidant pathway and attenuates murine tubular epithelial cell apoptosis2019

    • Author(s)
      Liu Chi、Fujino Masayuki、Zhu Shuoji、Isaka Yoshitaka、Ito Hidenori、Takahashi Kiwamu、Nakajima Motowo、Tanaka Tohru、Zhu Ping、Li Xiao‐Kang
    • Journal Title

      FEBS Open Bio

      Volume: 9 Issue: 11 Pages: 1928-1938

    • DOI

      10.1002/2211-5463.12729

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stem Cells as a Resource for Treatment of Infertility-related Diseases2019

    • Author(s)
      Wang Jing、Liu Chi、Fujino Masayuki、Tong Guoqing、Zhang Qinxiu、Li Xiao-Kang、Yan Hua
    • Journal Title

      Current Molecular Medicine

      Volume: 19 Issue: 8 Pages: 539-546

    • DOI

      10.2174/1566524019666190709172636

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hydrogen inhalation protects hypoxic-ischemic brain damage by attenuating inflammation and apoptosis in neonatal rats2019

    • Author(s)
      Wu Guojiao、Chen Zhiheng、Wang Peipei、Zhao Mingyi、Fujino Masayuki、Zhang Chen、Zhou Wenjuan、Hirano Shin-Ichi、Li Xiao-Kang、Zhao Lingling
    • Journal Title

      Experimental Biology and Medicine

      Volume: 244 Issue: 12 Pages: 1017-1027

    • DOI

      10.1177/1535370219855399

    • Related Report
      2019 Research-status Report
  • [Journal Article] 5‐ALA/SFC Attenuated Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats2019

    • Author(s)
      Liu Chi、Zhu Ping、Fujino Masayuki、Zhu Shuoji、Ito Hidenori、Takahashi Kiwamu、Nakajima Motowo、Tanaka Tohru、Zhuang Jian、Li Xiao‐Kang
    • Journal Title

      Alcoholism: Clinical and Experimental Research

      Volume: 43 Issue: 8 Pages: 1651-1661

    • DOI

      10.1111/acer.14117

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Salvianolic acid B ameliorates liver injury in a murine aGvHD model by decreasing inflammatory responses via upregulation of HO-12019

    • Author(s)
      Zhao Jing、Yang Xing-Chen、Fujino Masayuki、Ichimaru Naotsugu、Que Weitao、Li Xiao-Kang、Takahara Shiro
    • Journal Title

      Transplant Immunology

      Volume: 55 Pages: 101203-101203

    • DOI

      10.1016/j.trim.2019.03.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 5-aminolaevulinic acid (ALA), enhances heme oxygenase (HO)-1 expression and attenuates tubulointerstitial fibrosis and renal apoptosis in chronic cyclosporine nephropathy.2019

    • Author(s)
      Liu C, Zhu P, Fujino M, Isaka Y, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhuang J, Li XK
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 508 Issue: 2 Pages: 583-589

    • DOI

      10.1016/j.bbrc.2018.11.175

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Liver transplantation: New treatment for mucopolysaccharidosis type VI in rats.2019

    • Author(s)
      Toyama S, Migita O, Fujino M, Kunieda T, Kosuga M, Fukuhara Y, Nagahara Y, Li XK, Okuyama T.
    • Journal Title

      Pediatr Int

      Volume: 261 Issue: 2 Pages: 180-189

    • DOI

      10.1111/ped.13751

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Myeloid heme oxygenase-1 a new therapeutic target in anti-inflammation2018

    • Author(s)
      Zhao M, Yang M, Que W, Zhong L, Fujino M, Li XK.
    • Journal Title

      Frontiers in Bioscience

      Volume: 23 Issue: 11 Pages: 2001-2015

    • DOI

      10.2741/4685

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Combination of 5-aminolevulinic acid and iron prevents skin fibrosis in murine sclerodermatous graft-versus-host disease.2018

    • Author(s)
      Liu C, Yang X, Zhu P, Fujino M, Ito H, Takahashi K, Nakajima M, Tanaka T, Wang J, Zhuang J, Zou H, Li XK.
    • Journal Title

      Exp Dermatol.

      Volume: 10 Issue: 10 Pages: 1104-1111

    • DOI

      10.1111/exd.13730

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular hydrogen protects against ischemia-reperfusion injury in a mouse fatty liver model via regulating HO-1 and Sirt1 expression.2018

    • Author(s)
      Li S, Fujino M, Ichimaru N, Kurokawa R, Hirano S, Mou L, Takahara S, Takahara T, Li XK.
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 14019-14019

    • DOI

      10.1038/s41598-018-32411-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Development of new membrane fusion inhibitors against HIV-1 by “dimerization” strategy2018

    • Author(s)
      Murakami T, X Ebihara K, Fujino M, Honda Y, Kobayakawa T, Nomura W, Tamamura H
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 二量体化に基づいた新規抗HIV-1膜融合阻害薬の創出2018

    • Author(s)
      村上 努、海老原健人、藤野真之、本田柚奈、小早川拓也、野村 渉、玉村啓和
    • Organizer
      第32回日本エイズ学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ウイルスポリメラーゼの不可逆阻害を目指した新規2'-&βセレノ核酸アナログの創製2018

    • Author(s)
      村上 努、木村康明、新美結士、藤野真之、片倉秀雄、鈴木哲朗、児玉栄一、阿部 洋
    • Organizer
      第32回日本エイズ学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Characterization of novel HIV-1 inhibitors targeting Gag-TSG101 interaction2018

    • Author(s)
      Siarot Lowela、Chutiwitoonchai Nopporn、佐藤洋隆、Chang Hao、小谷 治、横山 勝、佐藤裕徳、藤野真之、村上 勉、近藤恭光、本田香 り、長田裕之、上田一樹、伊藤嘉浩、青野俊裕、児玉栄一、黒田和道、武井正美、間 陽子
    • Organizer
      第32回日本エイズ学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] エイズウイルス病原性における糖鎖の役割2018

    • Author(s)
      森 一泰、藤野真之
    • Organizer
      第5回糖鎖免疫研究会 Glyco-immunology 2019
    • Related Report
      2018 Research-status Report
  • [Presentation] Biological and molecular characterization of a novel anti-HIV-1 compound created by in silico design and de novo organic synthesis2018

    • Author(s)
      Murakami T, Fujino M, Yokoyama M, Kobayakawa T, Takeuchi H, Masuda T, Kotani O, Tamamura H, Sato H.
    • Organizer
      The 2018 Meeting on Retroviruses
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Astaxanthin Prevents Ischemia-Reperfusion Injury of the Steatotic Liver in Mice2018

    • Author(s)
      Li S, Takahara T, Fujino M Li XK, Takahara S
    • Organizer
      27th International Congress of The Transplantation Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Protective immune responses elicited by a live-attenuated SIV vaccine required for containment of heterologous SIV infection2018

    • Author(s)
      Mori K, Watanabe S, Fujino M, Okamura T, Sugimoto C
    • Organizer
      The 30th The International Workshop on Retroviral Pathogenesis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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