創薬標的の探索を目指したＩＬ－１関連遺伝子改変マウスライブラリーの作製と解析

2013 Fiscal Year Annual Research Report

• Project/Area Number: 24220011
• Research Institution: Tokyo University of Science
• Principal Investigator: 岩倉 洋一郎 東京理科大学, 生命医科学研究所, 教授 (10089120)
• Co-Investigator(Kenkyū-buntansha): 西城 忍 千葉大学, 真菌医学研究センター, 准教授 (60396877) ; 海部 知則 東京理科大学, 生命医科学研究所, 助教 (90343037)
• Project Period (FY): 2012-05-31 – 2017-03-31
• Keywords: 実験動物 / サイトカイン / C型レクチン

Research Abstract

IL-1関連遺伝子の機能解析としては、本年度は、IL-1R2KOマウスにおける関節炎増悪化について解析を行なった。現在、研究成果を纏めて、国際的な学術誌に投稿中である。また、IL-1RN欠損マウスにおいて、IL-1シグナルが過剰に入ることにより、T細胞において、炎症を収束させる役割を担う制御性T細胞のマスターレギュレーターであるFoxp3の発現が抑制され、Th17への分化を促進させることを明らかとした。この研究成果は、国際的な学術誌であるJ. Immunol.において公表することができた。加えて、IL-1RN欠損マウスをRAG2欠損背景に置き換えた時に、直腸脱肛後に死に至る重篤な腸炎を自然発症することを見出した。このマウスでは、近年、新たに同定された自然免疫リンパ球であるILC3からのIL-17A分泌が亢進しており、さらにIL-17Aを欠損させることにより、有意に腸炎の症状が緩和された。この成果も学術誌において報告することができた。C型レクチンファミリー分子の解析としては、現在、DCAR1,Clec12b欠損マウスおよびClec1a欠損マウスの表現解析を行なっている。また、DCIR2,DCAR2およびClec12a欠損マウスを作製中である。C1qtnfファミリー分子の解析については、IL-RN欠損マウスにおいて、顕著に発現亢進している遺伝子群として、C1qtnfファミリーを同定した。そのうちC1qtnf6欠損マウスにおいてコラーゲン誘導性関節炎が増悪化し、一方、C1qtnf6導入マウスにおいては関節炎が緩和された。また、C1qtnf3において、コラーゲン誘導性関節炎が増悪化することも明らかとした。この成果は、国際的な学術誌BIochem.Biophys.Res.Commun.にて公表することができた。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

本年度は、IL-1RN欠損マウスを用いた詳細な解析により、IL-1過剰シグナルが制御性T細胞の分化を抑制し、結果、Th17分化を促すことを明らかとし、国際的な学術誌にて、公表した。加えて、大腸炎の新たなモデルおよび発症メカニズムとして、過剰なIL-1シグナルが、近年注目されているILC3を介してIL17Aの分泌を制御し、大腸炎の病態へ関与していることが明らかとなった。今後も、さらなるIL-1シグナルの分子機序が同定できることが期待できる。また、C型レクチンファミリー分子およびC1qtnfファミリーにおいて、遺伝子欠損マウスを既に5系統、また、遺伝子導入マウスを1系統を樹立しており、遺伝子改変マウスライブラリーとしても順調に系統数を樹立している。創薬標的としては、C1qtnf6が有望であり、関節炎等の病態への治療効果および臨床応用を検討している。

Strategy for Future Research Activity

今後は、IL-1関連遺伝子の遺伝子改変マウスを作製し、さらなる系統の樹立を目指し、遺伝子改変マウスライブラリーのさらなる充実をはかる。また、機能解析についてもIL-1R2欠損マウス、C型レクチン遺伝子欠損マウスおよびC1qtnfファミリー遺伝子欠損マウス等を用いて、炎症応答への新たな分子機序の解明を目指す。創薬標的としてはC1qtnf6が有望であり、自己免疫疾患病態への治療効果を検討して行く予定である。現在、CRSPR/Cas9を用いた遺伝子欠損マウスの作製を試みており、今後、迅速に遺伝子改変マウスの作製が可能になり、研究課題の達成が加速されることが期待される。

Research Products

• [Journal Article] IL-17A as an inducer for Th2 immune responses in murine atopic dermatitits models. (2014)
  • Author(s): Nakajima, S., Kitoh, A., Egawa, G., Natsuaki, Y., Nakamizo, S., Sagita, Moniaga, C., Otsuka, A., Honda, T., Hanakawa, S., Amano, W., Iwakura, Y., Nakae, S., Kubo, M., Miyachi, Y., and Kabashima, K.
  • Journal Title: J. Invest. Dermatol. Volume: 134(8) Pages: 2122-2130
  • DOI: 10.1038
  • Peer Reviewed
• [Journal Article] Stage-specific roles for Cxcr4 signaling in murine hematopoietic stem/progenitor cells in the process of bone marrow repopulation. (2014)
  • Author(s): Lai, C. Y., Yamazaki, S., Okabe, M., Suzuki, S., Maeyama, Y., Iimura, Y., Onodera. M., Kakuta, S., Iwakura, Y., Nojima, M., Otsu, M., and Nakauchi, H.
  • Journal Title: Stem Cells Volume: 32(7) Pages: 1929-1942
  • DOI: 10.1002
  • Peer Reviewed
• [Journal Article] Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis. (2014)
  • Author(s): Song, X., Gao, H., Lin, Y., Yao, Y,. Zhu S, Wang J, Liu Y, Yao X, Meng G, Shen N, Shi Y, Iwakura Y, and Qian Y.
  • Journal Title: Immunity Volume: 40(1) Pages: 140-152
  • DOI: 10.1016
  • Peer Reviewed / Open Access
• [Journal Article] Defect of CARD9 leads to impaired accululation of IFN-g-producing memory-phenotype T cells in lungs and increased susceptibility to pulmonary infection with Cryptococcus neoformans. (2014)
  • Author(s): Yamamoto, H., Nakamura, Y., Sato, K., Takahashi, Y., Nomura, T., Miyasaka, T., Ishii, K., Hara, H., Yamamoto, N., Kanno, E., Iwakura, Y., and Kawakami, K.
  • Journal Title: Infect. Immun. Volume: 82(4) Pages: 1606-1615
  • DOI: 10.1128
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of Gr-1dull+ cellsin the production of TNF-a and IL-17 and exacerbated systemic inflammatory response caused by lipopolysaccharide. (2014)
  • Author(s): Tanno, D., Akahori, Y., Toyama, M., Sato, K., Kudo, D., Abe, Y., Miyasaka, T., Yamamoto, H., Ishii, K., Kanno, E., Maruyama, R., Kushimoto, S., Iwakura, Y., and Kawakami, K.
  • Journal Title: Inflammation Volume: 37 Pages: 186-195.
  • DOI: 10.1007/s10753-013-9729-5
  • Peer Reviewed
• [Journal Article] Mechanism of pro-tumorigenic effect of BMP-6: Neovascularizatioon involving tumor-associated macrophages and IL-1a. (2014)
  • Author(s): Kwon, S. J., Lee, G. T., Lee, J. H., Iwakura, Y., Kim, W. J., and Kim, I. Y.
  • Journal Title: Prostate Volume: 74 Pages: 121-133.
  • DOI: 10.1002/pros.22734.
  • Peer Reviewed
• [Journal Article] Positive feedback between NF-kB and TNF-a promotes leukemia-initiating cell capacity. (2014)
  • Author(s): Kagoya, Y., Yoshimi, A., Kataoka, K., Nakagawa, M., Kumano, K., Arai, S., Kobayashi, H., Saito, T., Iwakura, Y., and Kurokawa, M.
  • Journal Title: J. Clin. Invest. Volume: 124 Pages: 528-542
  • DOI: 10.1172/JCI68101.
  • Peer Reviewed
• [Journal Article] Critical role for inflammasome-independent IL-1b production in osteomyelitis. (2014)
  • Author(s): Lukens, J. R., Gross, J. M., Calabrese, C., Iwakura, Y., Lamkanfi, M., Vogel, P., and Kanneganti, T. D.
  • Journal Title: Proc. Natl. Acad. Sci. U. S. A. Volume: 111 Pages: 1066-1071
  • DOI: 10.1073/pnas.1318688111.
  • Peer Reviewed
• [Journal Article] Inflammasome-independent IL-1b mediates autoinflammatory diseases in Pstpip2-deficient mice. (2014)
  • Author(s): Cassel, S. L., Janczy, J. R., Bing, X., Wilson, S. P., Olivier, A. K., Otero, J. E., Iwakura, Y., Shayakhmetov, D. M., Bassuk, A. G., Abu-Amer, Y., Brogden, K. A., Burns, T. L., Sutterwala, F. S., and Ferguson, P. J.
  • Journal Title: Proc. Natl. Acad. Sci. U. S. A. Volume: 111 Pages: 1072-1077
  • DOI: 10.1073/pnas.1318685111.
  • Peer Reviewed
• [Journal Article] Excess IL-1 signaling enhances the development of Th17 cells by downregulating TGF-b-induced Foxp3 expression. (2014)
  • Author(s): Ikeda, S., Saijo, S., Murayama, M. A., Shimizu, K., Akitsu, A., and Iwakura, Y.
  • Journal Title: J. Immunol. Volume: 192 Pages: 1449-1458.
  • DOI: 10.4049/jimmunol.1300387.
  • Peer Reviewed
• [Journal Article] Dectin-2 regulates the effector phase of house dust mite-elicited pulmonary inflammation independently from its role in sensitization. (2014)
  • Author(s): Parsons, M. W., Li, L., Wallace, A. M., Lee, M. J., Katz, H. R., Fernandez, J. M., Saijo, S., Iwakura, Y., Austen, K. F., Kanaoka, Y., and Barrett, N. A.
  • Journal Title: J. Immunol. Volume: 192 Pages: 1361-1371.
  • DOI: 10.4049/jimmunol.1301809.
  • Peer Reviewed
• [Journal Article] Nonagonistic Dectin-1 ligand transforms GpG into a multiforms GpG into a multitask nanoparticlulate TLR9 agonist. (2014)
  • Author(s): Kobiyama. K., Aoshi, T., Narita, H., Kuroda, E., Hayashi, M., Tetsutani, K., Koyama, S., Mochizuki, S., Sakurai, K., Katakai, Y., Yasutomi, Y., Saijo, S., Iwakura, Y., Akira, S., Coban, C., and Ishii, K. J.
  • Journal Title: Proc. Natl. Acad. Sci. U. S. A. Volume: 111 Pages: 3086-3091.
  • DOI: 10.1073/pnas.1319268111.
  • Peer Reviewed
• [Journal Article] Ectopic cerebellar cell migration causes maldevelopment of purkinje cells and abnormal motor behavior in CXCR4 null mice. (2014)
  • Author(s): Huang, G. J., Edwards, A., Tsai, C. Y., Lee, Y. S., Peng, L., Era, T., Hirabayashi, Y., Tsai, C. Y., Nishikawa, S., Iwakura, Y., Chen, S. J., and Flint, J.
  • Journal Title: PLoS One Volume: 8 Pages: e86471
  • DOI: 10.1371/journal.pone.0086471.
  • Peer Reviewed
• [Journal Article] Rag2-deficient IL-1 receptor antagonist deficient mice are a novel colitis model in which innate lymphoid cell-derived IL-17 is involved in the pathogenesis. (2014)
  • Author(s): Akitsu A., Kakuta S., Saijo S., Iwakura Y.
  • Journal Title: Exp. Anim. Volume: 印刷中 Pages: -
  • Peer Reviewed
• [Journal Article] Dectin-2 promotes house dust mite-induced Th2 and Th17 cell differentiation and allergic airway inflammation in mice. (2014)
  • Author(s): Norimoto, A., Hirose, K., Iwata, A., Tamachi, T., Yokota, M., Takahashi, K., Saijo, S., Iwakura, Y., and Nakajima, H.
  • Journal Title: Am. J. Respir. Cell Mol. Biol. Volume: 印刷中 Pages: -
  • DOI: 10.1165/rcmb.2013-0522OC
  • Peer Reviewed
• [Journal Article] Intrahepatic innate lymphoid cells secrete IL-17A and IL-17F that are crucial for T cell priming in vial infection. (2014)
  • Author(s): Jie, Z., Liang, Y., Hou, L., Dong, C., Iwakura, Y., Soong, L., Cong, Y., and Sun, J.
  • Journal Title: J. Immunol. Volume: 192 Pages: 3289-3300
  • DOI: 10.4049/jimmunol.1303281.
  • Peer Reviewed
• [Journal Article] Multiple CD11c+ cells collaboratively express IL-1b to modulate stromal vascular endothelial growth factor and lymph node vascular-stromal growth. (2014)
  • Author(s): Benahmed, F., Chyou, S., Dasoveanu, D., Chen, J., Kumar, V., Iwakura, Y., and Lu, T. T.
  • Journal Title: J. Immunol. Volume: 印刷中 Pages: -
  • DOI: 10.4049/jimmunol.1301765.
  • Peer Reviewed
• [Journal Article] Regulatory T cells are strong promoters of acute ischemia stroke in mice by inducing dysfunction of the cerebral microvasculature. (2013)
  • Author(s): Kleinschnitz, C., Kraft, P., Dreykluft, A., Hagedorn, I., Gobel, K., Schuhmann, M. K., Langhauser, F., Helluy, X., Schwarz, T., Bittner, S., Mayer, C. T., Brede, M., Varallyay. C., Pham, M., Bendszus, M., Jakob, P., Magnus, T., Meuth, S. G., Iwakura, Y., Zernecke, A. et al.
  • Journal Title: Blood Volume: 121 Pages: 679-691
  • DOI: 10.1182/blood-2012-04-426734.
  • Peer Reviewed
• [Journal Article] IL-17A promotes macrophage effector mechanisms against Trypanosoma cruzi by trapping parasites in the endolysosomal compartment. (2013)
  • Author(s): Erdmann, H., RoBnagel, C., Bohme, J., Iwakura, Y., Jacobs, T., Schaible, U. E., and Holscher, C.
  • Journal Title: Immunobiology Volume: 218, Pages: 910-923
  • DOI: 10.1016/j.imbio.2012.10.005.
  • Peer Reviewed
• [Journal Article] Negative feedback on IL-23 exerted by IL-17A during pulmonary inflammation. (2013)
  • Author(s): Silverpil, E., Wright, A. K., Hansson, M., Jirholt, P., Henningsson, L., Smith, M. E., Gordon, S. B., Iwakura, Y., Gjertsson, I., Glader, P., and Linden, A.
  • Journal Title: Innate Immun. Volume: 19 Pages: 479-492
  • DOI: doi: 10.1177/1753425912470470.
  • Peer Reviewed
• [Journal Article] Vaspin inhibits apoptosis of endothelial cells as a ligand for cell-surface GRP78/VDAC complex. (2013)
  • Author(s): Nakatsuka, A., Wada, J., Iseda, I., Teshigawara, S., Higashio, K., Murakami, K., Kanzaki, M., Inoue, K., Terami, T., Katayama, A., Hida, K., Eguchi, J., Ogawa, D., Matsuki, Y., Hiramatsu, R., Yagita, H., Kakuta, S., Iwakura, Y., and Makino, H.
  • Journal Title: Circ. Res. Volume: 112 Pages: 771-780
  • DOI: 10.1161/CIRCRESAHA.111.300049
  • Peer Reviewed
• [Journal Article] IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice. (2013)
  • Author(s): Kurimoto, E., Miyahara, N., Kanehiro, A., Waseda, K., Taniguchi, A., Ikeda, G., Koga, H., Nishimori, H., Tanimoto, Y., Kataoka, M., Iwakura, Y., Gelfand, E. W., and Tanimoto, M.
  • Journal Title: Respir. Res. Volume: 14 Pages: 5
  • DOI: 10.1186/1465-9921-14-5
  • Peer Reviewed
• [Journal Article] Cyclosporine A drives a Th17- and Th2-mediated posttransplant obliterative airway disease. (2013)
  • Author(s): Lemaitre, P. H., Vokaer, B., Charbonnier, L. M., Iwakura, Y., Field, K. A., Estenne, M., Goldman, M., Leo, O., Remmelink, M., and Le Moine, A.
  • Journal Title: Am. J. Transplant. Volume: 13 Pages: 611-620
  • DOI: 10.1111/ajt.12067.
  • Peer Reviewed
• [Journal Article] Smap 1 deficiency perturbs receptor trafficking and predisposes mice to myelodyspasia. (2013)
  • Author(s): Kon, S., Minegishi, N., Tanabe, K., Watanabe, T., Funaki, T., Wong, W. F., Sakamoto, D., Higuchi, Y., Kiyonari, H., Asano, K., Iwakura. Y., Fukumoto, M., Osato, M., Sanada, M., Ogawa, S., Nakamura, T., and Satake, M.
  • Journal Title: J. Clin. Invest. Volume: 123 Pages: 1123-1137
  • DOI: 10.1172/JCI63711.
  • Peer Reviewed
• [Journal Article] MFGE8 inhibits inflammasome-induced IL-1b production and limits postischemic cerebral injury. (2013)
  • Author(s): Deroide, N., Li, X., Lerouet, D., Van Vre, E., Baker, L., Harrison, J., Poittevin, M. Masters, L., Nih, L., Margaill, I., Iwakura, Y., Ryffel, B., Pocard, M., Tedgui, A., Kubis, N., and Mallat, Z.
  • Journal Title: J. Clin. Invest. Volume: 123 Pages: 1176-1181
  • DOI: 10.1172/JCI65167.
  • Peer Reviewed
• [Journal Article] Hypoxia enhances innate immune activation to Aspergillus fumigatus through cell wall modulation. (2013)
  • Author(s): Shepardson, K. M., Ngo, L. Y., Aimanianda, V., Latge, J.-P., Barker, B. M., Blosser, S. J., Iwakura, Y., Hohl, T. M., and Cramer, R. A.
  • Journal Title: Microbe. Infect. Volume: 15 Pages: 259-269
  • DOI: 10.1016/j.micinf.2012.11.010.
  • Peer Reviewed
• [Journal Article] Mature dendritic cell suppression by IL-1 receptor antagonist on retinal pigment epithelium cells. (2013)
  • Author(s): Sugita, S., Kawazoe, Y., Imai, A., Usui, Y., Iwakura, Y., Isoda, K., Ito, M., and Mochizuki, M.
  • Journal Title: Invest. Ophthalmol. Vis. Sci. Volume: 54 Pages: 3240-3249
  • DOI: 10.1167/iovs.12-11483.
  • Peer Reviewed
• [Journal Article] C-typte lectin MCL is an FcRg-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor. (2013)
  • Author(s): Miyake, Y., Toyonaga. K., Mori, D., Kakuta, S., Hoshino, Y., Oyamada, A., Yamada, H., Ono, K. I., Suyama, M., Iwakura, Y., Yoshikai, Y., and Yamasaki, S.
  • Journal Title: Immunity Volume: 38 Pages: 1050-1062
  • DOI: 10.1016/j.immuni.2013.03.010.
  • Peer Reviewed
• [Journal Article] Neutrophils are essential as a source of IL-17 in the effector phase of arthritis. (2013)
  • Author(s): Katayama, M., Ohmura, K., Yukawa, N., Terao, C., Hashimoto, M., Yoshifuji, H., Kawabata, D., Fujii, T., Iwakura, Y., and Mimori, T.
  • Journal Title: PLoS One Volume: 8 Pages: e62231
  • DOI: 10.1371/annotation/5fedb3bf-c9c2-4862-9ad5-23c8ae484ad5
  • Peer Reviewed
• [Journal Article] Double deficiency in IL-17 and IFN-g signaling significantly suppresses the development of diabetes in the NOD mouse. (2013)
  • Author(s): Kuriya, G., Uchida, T., Akazawa, S., Kobayashi, M., Nakamura, K., Satoh, T., Horie, I., Kawasaki, E., Yamasaki, H., Yu, L., Iwakura, Y., Sasaki, H., Nagayama, Y., Kawakami, A., and Abiru, N.
  • Journal Title: Diabetologia Volume: 56 Pages: 1773-1780
  • DOI: 10.1007/s00125-013-2935-8.
  • Peer Reviewed
• [Journal Article] RIP1-driven autoinflammation targets IL-1a independently of inflammasomes and RIP3. (2013)
  • Author(s): Lukens, J. R., Vogel, P., Johnson, G. R., Kelliher, M. A., Iwakura, Y., Lamkanfi, M., and Kanneganti, T. D.
  • Journal Title: Nature Volume: 498 Pages: 224-227
  • DOI: 10.1038/nature12174.
  • Peer Reviewed
• [Journal Article] Obesity-induced gut microbial metabolite prootes liver cancer through senescence secretome. (2013)
  • Author(s): Yoshimoto, S., Loo, T. M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., Iwakura, Y., Oshima, K., Morita, H., Hattori, M., Honda, K., Ishikawa, Y., Hara, E., and Ohtani, N.
  • Journal Title: Nature Volume: 499 Pages: 97-101
  • DOI: 10.1038/nature13004.
  • Peer Reviewed
• [Journal Article] IL-23 protection against Plasmodium berghei infection in mice is partially dependent on IL-17 from macrophages. (2013)
  • Author(s): Ishida, H., Imai, T., Suzue, K., Hirai, M., Taniguchi, T., Yoshimura, A., Iwakura, Y., Okada, H., Suzuki, T., Shimokawa, C., and Hisaeda, H.
  • Journal Title: Eur. J. Immunol. Volume: 43 Pages: 2696-2706
  • DOI: 10.1002/eji.201343493.
  • Peer Reviewed
• [Journal Article] The Arf GAP SMAP2 is necessary for organized vesicle budding from the trans-Golgi-network and subsequent acrosome formation in spermaiogenesis. (2013)
  • Author(s): Funaki, T., Kon, S., Tanabe, K., Natsume, W., Sato, S., Shimizu, T., Yoshida, N., Wong, W. F., Ogura, A., Ogawa, T., Inoue, K., Ogonuki, N., Miki, H., Mochida. K., Endoh, K., Yomogida, K., Fukumoto, M., Horai, R., Iwakura, Y., Ito, C. et al.
  • Journal Title: Mol. Biol. Cell Volume: 24 Pages: 2633-2644
  • DOI: 10.1091/mbc.E13-05-0234.
  • Peer Reviewed
• [Journal Article] Pam3CSK4 enhanced beta cell loss and diabetogenesis: The roles of IFN-gamma and IL-17. (2013)
  • Author(s): Al Shamsi, M., Shahin, A., Iwakura, Y., Lukic, M. L., and Mensah-Brown, E. P.
  • Journal Title: Clin. Immunol. Volume: 149 Pages: 86-96
  • DOI: 10.1016/j.clim.2013.06.001.
  • Peer Reviewed
• [Journal Article] Interleukin-1b induced by Helicobacter pylori infection enhances mouse gastric carcinogenesis. (2013)
  • Author(s): Shigematsu, Y., Niwa, T., Rehnberg, E., Toyoda, T., Yoshida, S., Mori, A., Wakabayashi, M., Iwakura, Y., Ichinose, M., Kim, Y. J., and Ushijima, T.
  • Journal Title: Cancer Lett. Volume: 340 Pages: 141-147
  • DOI: 10.1016/j.canlet.2013.07.034.
  • Peer Reviewed
• [Journal Article] IL-17A mediates early post-translpant lesions agter teterotopic trachea allotransplantation in mice. (2013)
  • Author(s): Lemaitre, P. H., Vokaer, B., Charbonnier, L. M., Iwakura, Y., Estenne, M., Goldman, M., Leo, O., Remmelink, M., and Le Moine, A.
  • Journal Title: PLoS One Volume: 8 Pages: e70236
  • DOI: 10.1371/journal.pone.0070236.
  • Peer Reviewed
• [Journal Article] Generation of a mouse model with down-regulated U50 snoRNA (SN0RD50) expression and its organ-specific phenotypic modulation. (2013)
  • Author(s): Soeno, Y., Fujita, K., Kudo, T., Asagiri, M., Kakuta, S., Taya, Y., Shimazu, Y., Sato, K., Tanaka-Fujita, R., Kubo, S., Iwakura, Y., Nakamura, Y., Mori, S., and Aoba, T.
  • Journal Title: PLoS One Volume: 26 Pages: e72105
  • DOI: 10.1371/journal.pone.0072105.
  • Peer Reviewed
• [Journal Article] Fatty acid-inudced mitochondrial uncoupling elicits inflammasome-independent IL-1a and sterile vascular inflammation in atherosclerosis. (2013)
  • Author(s): Freigang, S., Ampenberger, F., Weiss, A., Kanneganti, T. D., Iwakura, Y., Hersberger, M., and Kopf, M.
  • Journal Title: Nat. Immunol. Volume: 14 Pages: 1045-1053
  • DOI: 10.1038/ni.2704.
  • Peer Reviewed
• [Journal Article] Genetic deletion of IL-17A reduces cigarette smoke-induced inflammation and alveolar type II cell apoptosis. (2013)
  • Author(s): Chang, Y., Al-Alwan, L., Audusseau, S., Chouiali, F., Carlevaro-Fita, J., Iwakura, Y., Baglole, C. J., Eidelman, D. H., and Hamid, Q.
  • Journal Title: Am. J. Physiol. Lung Cell Mol. Physiol. Volume: 306 Pages: L132-143
  • DOI: 10.1152/ajplung.00111.2013.
  • Peer Reviewed
• [Journal Article] Chronic follicular bronchiolitis requires antigen-specific regulatory T cell control to prevent fatal disease progression. (2013)
  • Author(s): Schmitt, E. G., Haribhai, D., Jeschke, J. C., Co, D. O., Ziegelbauer, J., Yan, K., Iwakura, Y., Mishra, M. K., Simpson, P., Salzman, N. H., and Williams, C. B.
  • Journal Title: J. Immunol. Volume: 191 Pages: 5460-5476
  • DOI: 10.4049/jimmunol.1301576.
  • Peer Reviewed
• [Journal Article] Colitogenic effector T cells: roles of gut-homing integrin, gut antigen specificity and gd T cells. (2013)
  • Author(s): Do, J. S., Visperas, A., Freeman, M. L., Iwakura, Y., Oukka, M., and Min, B.
  • Journal Title: Immunol. Cell Biol. Volume: 92 Pages: 90-98
  • DOI: 10.1038/icb.2013.70.
  • Peer Reviewed
• [Journal Article] Dectin-2-dependent NKT cell activation and serotype-specific antibody production in mice immunized with pneumococcal polysaccharide vaccine. (2013)
  • Author(s): Miyasaka, T., Akahori, Y., Toyama, M., Miyamura, N., Ishii, K., Saijo, S., Iwakura, Y., Kinjo, Y., Miyazaki, Y., Oishi, K., and Kawakami, K.
  • Journal Title: PLoS One Volume: 8 Pages: e78611
  • DOI: 10.1371/journal.pone.0078611.
  • Peer Reviewed
• [Journal Article] CTRP3 plays an important role in the development of collagen-induced arthritis in mice. (2013)
  • Author(s): Murayama, M. A., Kakuta, S., Maruhashi, T., Shimizu, K., Seno, A., Kubo, S., Sato, N., Saijo, S., Hattori, M., and Iwakura, Y.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 443 Pages: 42-48.
  • DOI: 10.1016/j.bbrc.2013.11.040.
  • Peer Reviewed
• [Journal Article] Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilliate obesity-associated airway hyperreactivity. (2013)
  • Author(s): Kim, H. Y., Lee, H. J., Chang, Y. J., Pichavant, M., Shore, S. A., Fitzgerald, K. A., Iwakura, Y., Israel, E., Bolger, K., Faul, J., Dekruyff, R. H., and Umetsu, D. T.
  • Journal Title: Nat. Med. Volume: 20 Pages: 54-61.
  • DOI: 10.1038/nm.3423.
  • Peer Reviewed
• [Journal Article] Transgenic expression of the human LEDGF/p75 gene relieves the species barrier against HIV-1 infection in mouse cells. (2013)
  • Author(s): Tada, T., Kadoki, M., Yang, L., Tokunaga, K. and Iwakura, Y.
  • Journal Title: Front. Microbiol. Volume: 4 Pages: 377.
  • DOI: 10.3389/fmicb.2013.00377
  • Peer Reviewed
• [Journal Article] Evaluation of Kampo medicines used to treat rheumatoid arthritis in collagen-induced arthritic and pX transgenic mice. (2013)
  • Author(s): Ono, Y., Ogihara, Y., Saijo, S., Iwakura, Y., and Inoue, M.
  • Journal Title: Mod. Rheumatol. Volume: 13 Pages: 50-56.
  • DOI: 10.3109/s101650300007.
  • Peer Reviewed
• [Journal Article] IL-22+CD4+T細胞による大腸炎誘導と抑制． (2013)
  • Author(s): 角木基彦、岩倉洋一郎
  • Journal Title: 臨床免疫・アレルギー科 Volume: 59 Pages: 405-410
• [Journal Article] 遺伝子改変マウスによる疾患発症機構の解析． (2013)
  • Author(s): 岩倉洋一郎
  • Journal Title: 感染・炎症・免疫 Volume: 43 Pages: 313-319
• [Presentation] Dectin-1の腸管免疫に果たす役割 (2014)
  • Author(s): 岩倉洋一郎
  • Organizer: 糖鎖免疫研究会Glyco-Immunology2014
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 20140214-20140214
  • Invited
• [Presentation] L-17およびTh17の自己免疫疾患に於ける役割 (2013)
  • Author(s): 岩倉洋一郎
  • Organizer: ノバルティスScientific Advisory Meeting, The Prince Tower
  • Place of Presentation: Sakura Tower Tokyo,高輪
  • Year and Date: 20131214-20131214
  • Invited
• [Presentation] 腸管免疫に於ける自然免疫の役割 (2013)
  • Author(s): 岩倉洋一郎
  • Organizer: 北海道大学遺伝子病制御研究所講演会
  • Place of Presentation: 北海道大学遺伝子病制御研究所
  • Year and Date: 20131111-20131111
  • Invited
• [Presentation] 自然免疫修飾による健康増進を目指した高機能食品開発の試み (2013)
  • Author(s): 岩倉洋一郎
  • Organizer: アグリビジネス創出フェア
  • Place of Presentation: 東京国際展示場
  • Year and Date: 20131025-20131025
  • Invited
• [Presentation] Dectin-1 signaling synergistically enhances toll-like receptor-mediated production of interferon beta. (2013)
  • Author(s): Kadoki, M., Sasaki, Y., Tang, C., Kamiya, T., and Iwakura, Y.
  • Organizer: 2013 Inaugural Meeting of the International Cytokine and Interferon Society (ICIS)
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20131002-20131002
• [Presentation] CCR8 deficiency causes exacerbation of contact hypersensitivity due to enhanced dendritic cell migration. (2013)
  • Author(s): Yabe, R. Shimizu, K. Shimizu, S. Azechi, S. Choi, BI. Kubo, S. Kakuta, S. Nakae, S. and Iwakura, Y.
  • Organizer: 2013 Inaugural Meeting of the International Cytokine and Interferon Society (ICIS)
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20131002-20131002
• [Presentation] 遺伝子欠損マウスを用いたIL-1の負の調節因子群の機能解析． (2013)
  • Author(s): 五十嵐哲郎、清水謙次、秋津葵、久保幸子、劉陽、中嶋明子、宝来玲子、石亀晴道、松本清司、久和茂、岩倉洋一郎、角田茂．
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜大、岐阜
  • Year and Date: 20130921-20130921
• [Presentation] 疾患モデルマウスを用いたIL1/IL17ファミリー遺伝子の腸管ポリープ形成における役割． (2013)
  • Author(s): 角田茂、鈴木俊佐、佐々木大和、五十嵐哲郎、渋川茉莉、村山正承、秋津葵、岡江寛明、石亀晴道、松本清司、久和茂、岩倉洋一郎．
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜大、岐阜
  • Year and Date: 20130921-20130921
• [Presentation] IL-17-producing gamma-delta T cells are crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice. (2013)
  • Author(s): Akitsu A., Ishigame H., Kakuta S., Saijo S., Iwakura Y.
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan, Italy
  • Year and Date: 20130824-20130824
• [Presentation] Pathways in inflammatory diseases (chair and speaker) (2013)
  • Author(s): Iwakura, Y.
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan, Italy
  • Year and Date: 20130823-20130823
  • Invited
• [Presentation] Dendritic Cell ImmunoReceptor (DCIR) is a negative regulator in balancing bone metabolism. (2013)
  • Author(s): Kaifu T., Maruhashi T, Ma G, Yabe R, Seno A, Iwakura Y.
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan, Italy
  • Year and Date: 20130823-20130823
• [Presentation] マウスを使った関節リウマチ治療法の研究 (2013)
  • Author(s): 岩倉洋一郎
  • Organizer: 免疫ふしぎ未来2013
  • Place of Presentation: 日本化学未来館
  • Year and Date: 20130811-20130811
  • Invited
• [Presentation] The Roles of IL-1 and IL-17 in the Development of Arthritis and Dermatitis in Animal Models (2013)
  • Author(s): Iwakura, Y.
  • Organizer: The 8th annual meeting of the Taiwaneese Society for Investigative Dermatology. Lecture Hall, Medical College of National Taiwan University (Shiou-Hwa Jee, President)
  • Place of Presentation: Taipei
  • Year and Date: 20130602-20130602
  • Invited
• [Presentation] Novel complement regulator CTRP6 effectively treats induced arthritis (2013)
  • Author(s): Iwakura, Y.
  • Organizer: JSICR-MMCB 2013 Joint Symposium in Tokyo, Toshi Center Hotel
  • Place of Presentation: Tokyo
  • Year and Date: 20130521-20130531
  • Invited
• [Presentation] インターロイキン－１受容体２型欠損マウスにおけるコラーゲン誘導関節炎の増悪化. (2013)
  • Author(s): 清水謙次、角田茂、溝呂木暁彦、宝来玲子、中嶋明子、岩倉洋一郎
  • Organizer: 第60回日本実験動物学会総会
  • Place of Presentation: つくば国際会議場
  • Year and Date: 20130515-20130515
• [Presentation] 炎症性大腸炎の病態形成におけるDectin-1の新規の役割解析. (2013)
  • Author(s): 唐策
  • Organizer: 第60回日本実験動物学会総会
  • Place of Presentation: つくば国際会議場
  • Year and Date: 20130515-20130515
• [Presentation] DCIR欠損マウスを用いたC型レクチン受容体による骨代謝制御機構の解明. (2013)
  • Author(s): 海部知則、丸橋拓海、馬光宇、矢部力朗、妹尾彬正、岩倉洋一郎.
  • Organizer: 第60回日本実験動物学会総会
  • Place of Presentation: つくば国際会議場
  • Year and Date: 20130515-20130515
• [Presentation] The roles of IL-17A and IL-17F in inflammation, tumorigenesis, and host defense against pathogens (2013)
  • Author(s): Iwakura, Y.
  • Organizer: Mackay Medical College, Taipei (Host: Nan-Chi Chan)
  • Place of Presentation: Taipei
  • Year and Date: 20130503-20130503
  • Invited
• [Presentation] The roles of IL-17A and IL-17F in inflammation, tumorigenesis, and host defense against pathogens (2013)
  • Author(s): Iwakura, Y.
  • Organizer: R & D Center for Biotech Products, National Ilan University, Ilan (Host: Wei-Jung Chen, Director & Prof., Kuo-Feng Hua)
  • Place of Presentation: Taipei
  • Year and Date: 20130503-20130503
  • Invited
• [Presentation] The roles of IL-17A and IL-17F in inflammation, tumorigenesis, and host defense against pathogens (2013)
  • Author(s): Iwakura, Y.
  • Organizer: Infection and Immunity Center, National Yang-Min University, Taipei (Host: Prof. Edmond Shie-Liang, Hsieh & Prof. Prof. Alice Chang)
  • Place of Presentation: Taipei
  • Year and Date: 20130502-20130502
  • Invited
• [Presentation] The roles of IL-17A and IL-17F in inflammation, tumorigenesis, and host defense against pathogens (2013)
  • Author(s): Iwakura, Y.
  • Organizer: College of Medicine, National Taiwan University, Taipei (Host: Prof. Shu-Wha Lin)
  • Place of Presentation: Taipei
  • Year and Date: 20130501-20130501
  • Invited
• [Presentation] The roles of IL-17A and IL-17F in inflammation, tumorigenesis, and host defense against pathogens (2013)
  • Author(s): Iwakura, Y.
  • Organizer: National Defense Medical Center, Taipei (Host: Prof. Ann Chen)
  • Place of Presentation: Taipei
  • Year and Date: 20130430-20130430
  • Invited
• [Presentation] Dcir-deficient mice as a novel model for ankylosing spondylitis (2013)
  • Author(s): 岩倉洋一郎
  • Organizer: 第57回日本リウマチ学会シンポジウム３
  • Place of Presentation: 京都国際会館
  • Year and Date: 20130418-20130418
  • Invited
• [Presentation] 新たな補体制御因子CTRP6の関節リウマチに対する治療効果 (2013)
  • Author(s): 村山正承、米沢朋、岩倉洋一郎.
  • Organizer: 第一回筑波大学・東京理科大学生命医科学研究所合同リトリート
  • Place of Presentation: 東京理科大学
  • Year and Date: 20130405-20130405
• [Book] サイトカインと自己免疫疾患．EXPERT膠原病・リウマチ 改訂第３版（住田孝之編） (2013)
  • Author(s): 角田茂、岩倉洋一郎
  • Total Pages: 33-38
  • Publisher: 診断と治療社
• [Patent(Industrial Property Rights)] CTRP3 plays an important role in the development of collagen-induced arthritis in mice. (2013)
  • Inventor(s): 岩倉洋一郎，村山正承
  • Industrial Property Rights Holder: 東京理科大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: US61/904,540
  • Filing Date: 2013-11-15
  • Overseas