Elucidation of the host's homeostatic responses by the regulation of immune system and its application to the prevention and treatment of immunological disorders

2017 Fiscal Year Annual Research Report

• Project/Area Number: 15H05787
• Research Institution: The University of Tokyo
• Principal Investigator: 谷口 維紹 東京大学, 生産技術研究所, 特任教授 (50133616)
• Co-Investigator(Kenkyū-buntansha): 岩倉 洋一郎 東京理科大学, 研究推進機構生命医科学研究所, 教授 (10089120) ; 柳井 秀元 東京大学, 生産技術研究所, 特任准教授 (70431765) ; 藤尾 圭志 東京大学, 医学部附属病院, 教授 (70401114) ; 根岸 英雄 東京大学, 生産技術研究所, 特任助教 (60514297) ; 西尾 純子 東京大学, 生産技術研究所, 特任助教 (40598679)
• Project Period (FY): 2015-05-29 – 2020-03-31
• Keywords: 免疫シグナル伝達 / 恒常性維持 / 自然免疫受容体 / HMGB1 / がん / 炎症 / 自己免疫疾患 / 免疫原性核酸

Outline of Annual Research Achievements

本研究は、自然免疫系を基軸とした生体の恒常性維持機構の解明と、その破綻がもたらす疾患の治療基盤の確立を目的としている。
HMGB1（High-mobility group box 1）について、in vitroで好中球がHMGB1に対する遊走能を示す知見を得、HMGB1は好中球遊走を介して炎症を促進していると考えられた。さらに、HMGB1の90番目のリシンがアセチル化を受けることを見出し、このリシン残基をアルギニンに置換したHMGB1変異体ノックインマウス（リシンのアセチル化が行えずHMGB1が細胞外に放出されない）を作製した。死細胞から放出されるDAMPsの探索を行い、免疫抑制性の新規DAMPs、PGE2（prostaglandin E2）を同定した。PGE2が、過剰な炎症を抑え臓器障害を抑制すること、また抗腫瘍応答を弱めることを明らかにした*。
IMF002（免疫抑制性化合物）の標的として低分子核内RNA（snRNA）を同定した。本snRNAがマウスやヒトのRAやSLEの血清中で有意に増加することを見出した。遺伝子欠損マウス、トランスジェニックマウスの作出に成功している。また、IMF003が抗腫瘍作用を示すことを発見し、その機構としてSTINGに依存的なシグナル経路の活性化によりI型IFN応答を誘導するという知見を得た。
胆嚢由来SP-Dが腸内細菌叢、及び腸管組織の恒常性維持に寄与していることを示した。一方で、腸炎罹患時には肝グルココルチコイド産生を介して胆嚢SP-D産生が亢進することを見出し、肝-胆-腸内細菌を基軸としたSP-Dを介する調節機構の存在を明らかにした*。
複数のC型レクチン受容体について、がん細胞排除機構への関与を検討した結果、Dectin-2が肝クッパー細胞を介して転移性肝がん細胞の排除に寄与していることを明らかにした*。（*は論文発表を行った）。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

炎症と密接に関連する好中球の遊走にHMGB1が重要であることを突き止めた。それによりHMGB1による炎症促進機構の一つが同定されたと考えられる。また、HMGB1を標的とするデコイ核酸ISM ODNが、種々の炎症モデルで病態を抑制する機構にも、好中球集積の低下が関与するという知見を得た。すなわち、DAMPsとして知られているHMGB1の機能の一端を明らかにできた。
また、新規DAMPsの同定についても成功しており、免疫抑制性DAMPとしてPGE2を同定した。臓器障害やがんの増大に重要であることを明らかにし、一連の結果を論文として発表している。またさらに、死細胞から放出される新規炎症性DAMPを同定し、その機能解析を進めており、予定以上の成果が出ている。
IMF002の標的であるsnRNAがマウス、ヒトにおけるSLE、関節リウマチの血清中で有意に増加することを見出し、IMF002がこれらの疾患モデルで病態を抑制することを突き止めている。snRNAのトランスジェニックマウス及びコンディショナル欠損マウスを作成し、このsnRNAの炎症誘導の分子機構を解析しており、これらの病態発症、増悪のメカニズムの一端が明らかにできるものと期待される。
腸管恒常性の維持においては、胆嚢由来SP-Dが腸管内で細菌叢を制御することにより消化管の恒常性が維持されていること証明し、今年度論文発表した。
また、C型レクチン受容体についてがん細胞排除への関与については、予定通りDectin-2、Mincle、Mclを検討し、Kupffer細胞に特異的に発現するDectin-2を介して肝転移がん細胞を貪食し排除するという機構を新たに見出し論文として公表した。
このように、新知見が多数得られている状況であり、本研究課題の予定期間内において、さらに発展が見込める状況である。よって、上記のように判断した。

Strategy for Future Research Activity

今後の研究の推進方策について、基本的には申請時の研究計画に沿って推進する。新展開が見られた際、または技術的困難が生じた場合には、代替法の検討などにより、適宜解決し、研究を推進していく予定である。これまでのところでは検討を進める上で大きな支障は生じていない。
HMGB1と炎症との関わりについては、HMGB1による好中球の遊走促進の病態モデルにおける重要性について検討していく。HMGB1の機能を阻害するISM ODNについても、病態の抑制と好中球の遊走との関連について検討を進めていく予定である。炎症促進性の新規DAMPsについて、その機能解析を進めており、ノックアウトマウスの作成を進めていく予定である。
ncRNAについてはノックアウトマウス、トランスジェニックマウスの作成が完了したことから、マウス個体を用いて、病態モデルにおけるncRNAの役割について検討を進める。胆嚢由来SP-Dが腸管内で細菌叢を制御することにより消化管の恒常性が維持されていることがわかった。本研究から派生した課題として、胆嚢由来の他の抗菌分子の解析、SP-D欠損によってもたらされるdysbiosisがどのような機構で腸管組織恒常性の破綻を来たすかについての解析、などを検討していきたい。Dectin-1キメラマウスについても、免疫監視、恒常性維持との関連について、検討を進めていく予定である。
一連の検討を通して、免疫系による恒常性維持システムの解明とその制御法の開発により、疾患の治療基盤の確立を目指していく。

Research Products

• [Journal Article] Establishment and analysis of a novel mouse line carrying a conditional knockin allele of a cancer-specific FBXW7 mutation. (2018)
  • Author(s): Ikenoue, T., Terakado, Y., Zhu, C., Liu, X., Ohsugi, T., Matsubara, D., Fujii, T., Kakuta, S., Kubo, S., Shibata, T., Yamaguchi, K., Iwakura, Y., and Furukawa, Y.
  • Journal Title: Sci. Rep. Volume: 8 Pages: 2021
  • DOI: 10.1038/s41598-018-19769-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] HER2 overexpression triggers an IL-1α pro-inflammatory circuit to drive tumorigenesis and promote chemotherapy resistance. (2018)
  • Author(s): Liu, S., Lee, J. S., Jie, C., Park, M. H., Iwakura, Y., Patel, Y., Soni, M., Reisman, D., and Chen, H.
  • Journal Title: Cancer Res. Volume: - Pages: -
  • DOI: 10.1158/0008-5472.CAN-17-2761
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] IL-1R2 deficiency suppresses dextran sodium sulfate-induced colitis in mice via regulation of microbiota. (2018)
  • Author(s): Yoshida, K., Murayama, M., Shimizu, K., Tang, C., Katagiri, N., Matsuo, K., Fukai F., and Iwakura, Y.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 496 Pages: 934-940
  • DOI: 10.1016/j.bbrc.2018.01.116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] NK cells control tumor-promoting function of neutrophils in mice. (2018)
  • Author(s): Ogura, K., Sato-Matsushita, M., Yamamoto, S., Hori, T., Sasahara, M., Iwakura, Y., Saiki, I., Tahara, H., and Hayakawa, Y.
  • Journal Title: Cancer Immunol. Res. Volume: - Pages: -
  • DOI: 10.1158/2326-6066.CIR-17-0204
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Splicing variant of WDFY4 augments MDA5 signalling and the risk of clinically amyopathic dermatomyositis. (2018)
  • Author(s): Kochi, Y., et. al.
  • Journal Title: Ann Rheum Dis. Volume: - Pages: -
  • DOI: 10.1136/annrheumdis-2017-212149
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Interferon (IFN) Class of Cytokines and the IFN Regulatory Factor (IRF) Transcription Factor Family. (2017)
  • Author(s): Negishi, H., Taniguchi, T., Yanai, H.
  • Journal Title: Cold Spring Harb Perspect Biol. Volume: - Pages: -
  • DOI: 10.1101/cshperspect.a028423
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fine-tuning type I IFN signaling: A new chapter in the IFN saga. (2017)
  • Author(s): Yanai, H., Taniguchi, T.
  • Journal Title: Cell Res. Volume: 27 Pages: 1407-1408
  • DOI: 10.1038/cr.2017.118
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gallbladder-derived surfactant protein D regulates gut commensal bacteria for maintaining intestinal homeostasis. (2017)
  • Author(s): Sarashina-Kida, H., Negishi, H., Nishio, J., Suda, W., Nakajima, Y., Yasui-Kato, M., Iwaisako, K., Kang, S., Endo, N., Yanai, H., Asagiri, M., Kida, H., Hattori, M., Kumanogo, A., and Taniguchi, T.
  • Journal Title: Proc Natl Acad Sci U. S. A. Volume: 114 Pages: 10178-10183
  • DOI: 10.1073/pnas.1712837114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of a novel site-specific pegylated interferon beta for antiviral therapy for chronic hepatitis B virus. (2017)
  • Author(s): Tsuge, M., Uchida, T., Hiraga, N., Kan, H., Makokha, G. N., Abe-Chayama, H., Miki, D., Imamura, M., Ochi, H., Hayes, C. N., Shimozono, R., Iwamura, T., Narumi, H., Suzuki, T., Kainoh, M., Taniguchi, T., Chayama, K.
  • Journal Title: Antimicrob Agents Chemother. Volume: 24 Pages: 61
  • DOI: 10.1128/AAC.00183-17
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A novel pegylated IFN-β as strong suppressor of the malignant ascites in a peritoneal metastasis model of human cancer. (2017)
  • Author(s): Iwamura, T., Narumi, H., Suzuki, T., Yanai, H., Mori, K., Yamashita, K., Tsushima, Y., Asano, T., Izawa, A., Momen, S., Nishimura, K., Tsuchiyama, H., Uchida, M., Yamashita, Y., Okano, K., Taniguchi, T.
  • Journal Title: Cancer Science Volume: 108 Pages: 581-589
  • DOI: 10.1111/cas.13176
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Brain interleukin-1 facilitates learning of a water maze spatial memory task in young mice. (2017)
  • Author(s): Takemiya, T., Fumizawa, K., Yamagata, K., Iwakura, Y., Kawakami, M.
  • Journal Title: Front Behav Neurosci. Volume: 11 Pages: 202
  • DOI: 10.3389/fnbeh.2017.00202
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] LC3-associated phagocytosis is required for dendritic cell inflammatory cytokine response to gut commensal yeast Saccharomyces cerevisiae. (2017)
  • Author(s): Lamprinaki, D., Beasy, G., Zhekova, A., Wittmann, A., James, S., Dicks, J., Iwakura, Y., Saijo, S., Wang, X., Chow, C. W., Roberts, I., Korcsmaros, T., Mayer, U., Wileman, T., and Kawasaki, N.
  • Journal Title: Front. Immunol. Volume: 8 Pages: 1397
  • DOI: 10.3389/fimmu.2017.01397
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Production of low-molecular weight soluble yeast β-glucans by an acid degradation method. (2017)
  • Author(s): Ishimoto, Y., Ishibashi, K. I., Yamanaka, D., Adachi, Y., Kanzaki, K., Iwakura, Y., and Ohno, N.
  • Journal Title: Int. J. Biol. Macromol. Volume: 107 Pages: 2269-2278
  • DOI: 10.1038/mi.2017.86
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neutralization of either IL-17A or IL-17F is sufficient to inhibit house dust mite induced allergic asthma in mice. (2017)
  • Author(s): Chenuet, P., Fauconnier, L., Madouri. F., Marchiol, T., Rouxel, N., Ledru, A., Mauny, P., Lory, R., Uttenhove, C., van Snick. J., Iwakura, Y., di Padova, F., Quesniaux, V., Togbe, D., and Ryffel, B.
  • Journal Title: Clin. Sci. (Lond) Volume: 131 Pages: 2533-2548
  • DOI: 10.1042/CS20171034
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] IL-17A contributes to reducing IFN-γ/IL-4 ratio and persistence of Entamoeba histolytica during intestinal amebiasis. (2017)
  • Author(s): Deloer, S., Nakamura, R., Kikuchi, M., Moriyasu, T., Kalenda, Y. D. J., Mohammed, E. S., Senba, M., Iwakura, Y., Yoshida, H., and Hamano, S.
  • Journal Title: Parasitol. Int. Volume: 66 Pages: 817-823
  • DOI: 10.1016/j.parint.2017.09.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] IL-17A-deficient mice are highly susceptible to Toxoplasma gondii infection due to excessively induced T. gondii HSP70 and IFN-γ production. (2017)
  • Author(s): Moroda, M., Takamoto, M., Iwakura, Y., Nakayama, J., and Aosai, F.
  • Journal Title: Infect. Immun. Volume: 85 Pages: 00399-17
  • DOI: 10.1128/IAI.00399-17
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The mycobacterial phosphatase PtpA regulates the expression of host genes and promotes cell proliferation. (2017)
  • Author(s): Wang, J., Ge, P., Qiang, L., Tian, F., Zhao, D., Chai, Q., Zhu, M., Zhou, R., Meng, G., Iwakura, Y., Gao, G. F., and Liu, C. H.
  • Journal Title: Nat. Commun. Volume: 8 Pages: 244
  • DOI: 10.4049/jimmunol.1700655
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fungal-derived cues promote ocular autoimmunity through a Dectin-2/Card9-mediated mechanism. (2017)
  • Author(s): Brown, B. R., Lee, E. J., Snow, P. E., Vance, E. E., Iwakura, Y., Ohno, N., Miura, N., Lin, X., Brown, G. D., Wells, C. A., Smith, J. R., Caspi, R. R., and Rosenzweig, H. L.
  • Journal Title: Clin. Exp. Immunol. Volume: 190 Pages: 293-303
  • DOI: 10.1111/cei.13021
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An ocular commensal protects from corneal infection by driving an IL-17 response from mucosal γδT cells. (2017)
  • Author(s): St Leger, A. J., Desal, J. V., Drummond, R. A., Kugadas, A., Almaghrabi, F., Silver, P., Raychaudhuri, K., Gadjeva, M., Iwakura, Y., Lionakis, M., and Caspi, R. R.
  • Journal Title: Immunity Volume: 47 Pages: 148-158
  • DOI: 10.1016/j.immuni.2017.06.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nociceptors boost the resolution of fungal osteoinflammation via the TRP channel-CGRP-Jdp2 axis. (2017)
  • Author(s): Maruyama, K., Takayama, Y., Kondo, T., Ishibashi, K. I., Sahoo, B. R., Kanemaru, H., Kumagai, Y., Martino, M. M., Tanaka, H., Ohno, N., Iwakura, Y., Takemura, N., Tominaga, M., and Akira, S.
  • Journal Title: Cell Rep. Volume: 19 Pages: 2730-2742
  • DOI: 10.1016/j.celrep.2017.06.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Protein tyrosine phosphatase δ mediates the Sema3A-induced cortical basal dendritic arborization through the activation of Fyn tyrosine kinase. (2017)
  • Author(s): Nakamura, F., Okada, T., Shishikura, M., Uetani, N., Taniguchi, M., Yagi, T., Iwakura, Y., Ohshima, T., Goshima, Y., and Strittmatter, S. M.
  • Journal Title: J. Neurosci. Volume: 37 Pages: 7125-7139
  • DOI: 10.1523/JNEUROSCI.2519-16.2017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Thermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling. (2017)
  • Author(s): Giles, D. A., et.al.
  • Journal Title: Nat. Med. Volume: 23 Pages: 829-838
  • DOI: 10.1038/nm.4346
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Modulation of an innate immune response by soluble yeast β-glucan prepared by a heat degradation method. (2017)
  • Author(s): Ishimoto, Y., Ishibashi, K. I., Yamanaka, D., Adachi, Y., Kanzaki, K., Okita, K., Iwakura, Y., and Ohno, N.
  • Journal Title: Int. J. Biol. Macromol. Volume: 104 Pages: 367-376
  • DOI: 10.1016/j.ijbiomac.2017.06.036
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Macrophage-derived IL-1α promotes sterile inflammation in a mouse model of acetaminophen hepatotoxicity. (2017)
  • Author(s): Zhang, C., Feng, J., Du, J., Zhuo, Z., Yang, S., Zhang, W., Wang, W., Zhang, S., Iwakura, Y., Meng, G., Fu, Y. X., Hou, B., and Tang, H.
  • Journal Title: Cell. Mol. Immunol. Volume: - Pages: -
  • DOI: 10.1038/cmi.2017.22
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Phospholipase Cδ1 regulates p38 MAPK activity and skin barrier integrity. (2017)
  • Author(s): Kanemaru, K., Nakamura, Y., Totoki, K., Fukuyama, T., Shoji, M., Kaneko, H., Shiratori, K., Yoneda, A., Inoue, T., Iwakura, Y., Kabashima, K., and Fukami, K.
  • Journal Title: Cell Death Differ. Volume: 24 Pages: 1079-1090
  • DOI: 10.1038/cdd.2017.56
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Megakaryocytes compensate for Kit insufficiency in murine arthritis. (2017)
  • Author(s): Cunin, P., Penke, L. R., Thon, J. N., Monach, P. A., Jones, T., Chang, M. H., Chen, M. M., Melki, I., Lacroix, S., Iwakura, Y., Ware, J., Gurish, M. F., Italiano, J. E., Boilard, E., and Nigrovic, P. A.
  • Journal Title: J. Clin. Invest. Volume: 27 Pages: 1714-1724
  • DOI: 10.1172/JCI84598
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elevation of pro-inflammatory cytokine levels following anti-resorptive drug treatment is required for osteonecrosis development in infectious osteomyelitis. (2017)
  • Author(s): Morita, M., Iwasaki, R., Sato, Y., Kobayashi, T., Watanabe, R., Oike, T., Nakamura, S., Keneko, Y., Miyamoto, K., Ishihara, K., Iwakura, Y., Ishii, K., Matsumoto, M., Nakamura, M., Kawana, H., Nakagawa, T., and Miyamoto, T.
  • Journal Title: Sci. Rep. Volume: 7 Pages: 46322
  • DOI: 10.1038/srep46322
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dectin-2 deficiency modulates Th1 differentiation and improves wound healing after myocardial infarction. (2017)
  • Author(s): Yan, X., Zhang, H., Fan, Q., Hu, J., Tao, R., Chen, Q., Iwakura, Y., Shen, W., Lu, L., Zhang, Q., and Zhang, R.
  • Journal Title: Circ. Res. Volume: 120 Pages: 1116-1129
  • DOI: 10.1161/CIRCRESAHA.116.310260
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Advanced glycation end products induce brain-derived neurotrophic factor release from human plateltets through the Src-family kinase activation. (2017)
  • Author(s): Furukawa, K., Fuse, I., Iwakura, Y., Sotoyama, H., Hanyu, O., Nawa, H., Sone, H., and Takei, N.
  • Journal Title: Cardiovasc. Diabetol. Volume: 16 Pages: 20
  • DOI: 10.1186/s12933-017-0505-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Overview of LAG-3-Expressing, IL-10-Producing Regulatory T Cells. (2017)
  • Author(s): Fujio, K., Yamamoto, K., and Okamura, T.
  • Journal Title: Curr Top Microbiol Immunol. Volume: 410 Pages: 29-45
  • DOI: 10.1007/82_2017_59
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Increased serum concentrations of IL-1 beta, IL-21 and Th17 cells in overweight patients with rheumatoid arthritis. (2017)
  • Author(s): Shoda, H., Nagafuchi, Y., Tsuchida, Y., Sakurai, K., Sumitomo, S., Fujio, K., and Yamamoto, K.
  • Journal Title: Arthritis Res Ther. Volume: 19 Pages: 111
  • DOI: 10.1186/s13075-017-1308-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis. (2017)
  • Author(s): Ishigaki, K., Kochi, Y., Suzuki, A., Tsuchida, Y., Tsuchiya, H., Sumitomo, S., Yamaguchi, K., Nagafuchi, Y., Nakachi, S., Kato, R., Sakurai, K., Shoda, H., Ikari, K., Taniguchi, A., Yamanaka, H., Miya, F., Tsunoda, T., Okada, Y., Momozawa, Y., Kamatani, Y., Yamada, R., Kubo, M., Fujio, K., and Yamamoto, K.
  • Journal Title: Nat. Genet. Volume: 49 Pages: 1120-1125
  • DOI: 10.1038/ng.3885
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Interleukin-10-producing LAG3+ regulatory T cells are associated with disease activity and abatacept treatment in rheumatoid arthritis. (2017)
  • Author(s): Nakachi, S., Sumitomo, S., Tsuchida, Y., Tsuchiya, H., Kono, M., Kato, R., Sakurai, K., Hanata, N., Nagafuchi, Y., Tateishi, S., Kanda, H., Okamura, T., Yamamoto, K., and Fujio, K.
  • Journal Title: Arthritis Res. Ther. Volume: 19 Pages: 97
  • DOI: 10.1186/s13075-017-1309-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TGF-β3 Inhibits Antibody Production by Human B Cells. (2017)
  • Author(s): Tsuchida, Y., Sumitomo, S., Ishigaki, K., Suzuki, A., Kochi, Y., Tsuchiya, H., Ota, M., Komai, T., Inoue, M., Morita, K., Okamura, T., Yamamoto, K., and Fujio, K.
  • Journal Title: PLoS One Volume: 12 Pages: 0169646
  • DOI: 10.1371/journal.pone.0169646
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of tonsillar CD4+CD25-LAG3+ T cells as naturally occurring IL-10-producing regulatory T cells in human lymphoid tissue. (2017)
  • Author(s): Sumitomo, S., Nakachi, S., Okamura, T., Tsuchida, Y., Kato, R., Shoda, H., Furukawa, A., Kitahara, N., Kondo, K., Yamasoba, T., Yamamoto, K., and Fujio, K.
  • Journal Title: J Autoimmun. Volume: 76 Pages: 75-84
  • DOI: 10.1016/j.jaut.2016.09.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 炎症性疾患発症におけるIL－17の役割 (2017)
  • Author(s): 岩倉洋一郎
  • Organizer: 第221回日本皮膚科学会熊本地方会
  • Invited
• [Presentation] 炎症性疾患および免疫系の恒常性維持におけるIL－17の役割 (2017)
  • Author(s): 岩倉洋一郎
  • Organizer: ノバルティスTAPの会
  • Invited
• [Presentation] 腸管免疫の恒常性維持におけるC型レクチンおよびIL－17Fの役割 (2017)
  • Author(s): 岩倉洋一郎
  • Organizer: 日本生物学研究所セミナー
  • Invited
• [Presentation] 炎症性疾患および免疫系の恒常性維持におけるIL－17の役割 (2017)
  • Author(s): 岩倉洋一郎
  • Organizer: 乾癬エキスパートミーティング in 関東甲信越
  • Invited
• [Presentation] Immune and Bone Metabolic Abnormalities in Dcir-deficient Mice. (2017)
  • Author(s): 岩倉洋一郎
  • Organizer: 日本骨代謝学会 学会合同シンポジウム
  • Invited
• [Presentation] 炎症性疾患発症におけるIL－17の役割 (2017)
  • Author(s): 岩倉洋一郎
  • Organizer: 日本炎症再生医学会
  • Invited
• [Presentation] 食品の腸内環境に及ぼす影響と疾病との関連 (2017)
  • Author(s): 岩倉洋一郎
  • Organizer: 第26回日本臨床環境医学会
  • Invited
• [Presentation] 炎症応答におけるIL－17の役割 (2017)
  • Author(s): 岩倉洋一郎
  • Organizer: 埼玉IL－17Aフォーラム
  • Invited
• [Presentation] Role of HMGB1 in inflammation and immunity; implication in transplantation (2017)
  • Author(s): Tadatsugu Taniguchi
  • Organizer: 2017 Seoul Forum
  • Int'l Joint Research / Invited
• [Presentation] Virtue and vice of the immune system: Self-derived molecules and molecular mechanisms that underlie the regulation of inflammation and cancer. (2017)
  • Author(s): Tadatsugu Taniguchi
  • Organizer: Consortium of Biological Sciences 2017
  • Int'l Joint Research / Invited
• [Presentation] Regulation of inflammation and tumor growth by DAMPs. (2017)
  • Author(s): Tadatsugu Taniguchi
  • Organizer: 2017 SAB Meeting of Tsinghua Institute for Immunology
  • Int'l Joint Research / Invited
• [Presentation] From Type I IFN to HMGB1 and other DAMP molecules: Regulators of immunity, inflammation and cancer. (2017)
  • Author(s): Tadatsugu Taniguchi
  • Organizer: International Cytokine Interferon Society Meeting (ICIS)
  • Int'l Joint Research / Invited
• [Presentation] From Qβ to another phage: Regulation of intestinal inflammation by a new bacteriophage. (2017)
  • Author(s): Tadatsugu Taniguchi
  • Organizer: The End of the Beginning, Symposium of Molecular Biology Zurich
  • Int'l Joint Research / Invited
• [Presentation] DAMPs, inflammation and cancer. (2017)
  • Author(s): Tadatsugu Taniguchi
  • Organizer: 2017 Changchun Forum on Research of Immunology and Disease
  • Int'l Joint Research / Invited
• [Presentation] Innate immune receptors in the regulation of tumor immunity. (2017)
  • Author(s): Tadatsugu Taniguchi
  • Organizer: Immuno-Oncology Summit 2017
  • Int'l Joint Research / Invited
• [Presentation] HMGB1 and other DAMPs in the regulation of inflammation and cancer. (2017)
  • Author(s): Tadatsugu Taniguchi
  • Organizer: Cancer, Inflammation, and Immunity
  • Int'l Joint Research / Invited
• [Presentation] The role of Dectin-1-IL-17F axis in the homeostasis of the intestinal immune system. (2017)
  • Author(s): Yoichiro Iwakura
  • Organizer: International Cytokine Interferon Society Meeting (ICIS)
  • Int'l Joint Research / Invited
• [Presentation] The role of Dectin-1-IL-17F axis in the homeostasis of the intestinal immune system. Inner Cosmos of the Body-Immunity, Tumors and Inflammation- (2017)
  • Author(s): Yoichiro Iwakura
  • Organizer: International Symposium of the Center for Animal Disease Models 2017
  • Int'l Joint Research / Invited
• [Presentation] Dectins and IBD Fungi/Dectins and mucosal immunity (2017)
  • Author(s): Yoichiro Iwakura
  • Organizer: 18th International Congress of Mucosal Immunity (ICMI2017)
  • Int'l Joint Research / Invited
• [Presentation] Novel animal models in arthritis Novel Animal Models in Rheumatoid Arthritis (2017)
  • Author(s): Yoichiro Iwakura
  • Organizer: Joint EULAR-APLAR session, EULAR
  • Int'l Joint Research / Invited
• [Presentation] Roles of C-type lectins in the immune system (2017)
  • Author(s): Yoichiro Iwakura
  • Organizer: BI/Kyoto University Symposium
  • Int'l Joint Research / Invited
• [Remarks] UTokyo Research: がんの肝転移を抑える新たなしくみを発見
  • URL: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/newly-discovered-mechanism-prevents-spread-of-cancer-to-liver.html
• [Remarks] UTokyo Research: 死んだ細胞から放出される免疫抑制分子を同定
  • URL: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/dead-cell-derived-immunosuppressive-molecule-identified.html