The roles of cytokines in the development of autoimmune deseases

2009 Fiscal Year Final Research Report

• Project/Area Number: 19059006
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: IWAKURA Yoichiro The University of Tokyo, 医科学研究所, 教授 (10089120)
• Co-Investigator(Kenkyū-buntansha): SAIJO Shinobu 東京大学, 医科学研究所, 助教 (60396877) ; KAKUTA Shigeru 東京大学, 医科学研究所, 助教 (80345032) ; FUJIKADO Noriyuki 東京大学, 医科学研究所, 助教 (90447334)
• Project Period (FY): 2007 – 2009
• Keywords: IL-1 / IL-17 / 疾患モデル動物 / ノックアウトマウス / C型レクチン

Research Abstract

Rheumatoid arthritis (RA) is one of the most serious medical problems worldwide with approximately 1% of the people in the world affected. The disease is autoimmune in nature and characterized by chronic inflammation of the synovial tissues in multiple joints. High levels of inflammatory cytokine expression in the joints are characteristics of the disease, although the pathogenesis has not been elucidated completely. We have been studying the pathogenesis of the disease using two arthritis models that we originally developed ; HTLV-I transgenic (HTLV-I Tg) mice and IL-1 receptor antagonist-deficient (IL-1Ra KO) mice. In this study, we analyzed the roles of IL-17 family cytokines in the development of autoimmune diseases and the mechanisms of Th17 induction through DC activation. We found that 1) IL-17A, but not IL-17F, plays an important role in the development of autoimmune diseases and inflammatory diseases, 2) Both IL-17A and IL-17F play important roles in the host defense against bacterial infections, 3) Both Dectin-1 and Dectin-2, which is a receptor for β-glucans and α-mannans, respectively, on DCs, induce Th17 differentiation through activation of DCs, and play important role in the host defense against fungal infections. These findings should be of use for the development of new therapeutics against autoimmune diseases and fungal infection.

Research Products

• [Journal Article] Tumor-infiltrating IL-17-producing gammadelta T cells spport the progression of tumor via promoting angiogenesis. (2010)
  • Author(s): Wakita, D., Sumida, K., Iwakura, Y., Nishikawa, H., Ohkuri, T., Chamoto, K., Kitamura, H., Nishimura, T.
  • Journal Title: Eur. J. Immunol. 15(Epub ahead of print)
• [Journal Article] Stem cell mobilization with G-CSF induces Type-17 differentiation and promotes scleroderma. (2010)
  • Author(s): Hill, G.R., Olver, S.D., Kuns, R.D., Varelias, A., Raffelt, N.C., Don, A.L.J., Markey, K.A., Wilson, Y.A., Smyth, M.J., Iwakura, Y., Tocker, J., Clouston, A., MacDonald, K.P.A.
  • Journal Title: Blood 30(Epub ahead of print)
• [Journal Article] IFN-γregulates the requirement for IL-17 in proteoglycan-induced arthritis. (2010)
  • Author(s): Doodes, P.D., Cao, Y., Hamel, K.M., Wang, Y., Rodeghero, R.I., Mikecz, K., Glant T.T., Iwakura, Y., Finnegan, A.
  • Journal Title: J. Immunol. 184 Pages: 1552-1559
• [Journal Article] Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. (2010)
  • Author(s): Madhur, M.S., Lob, H.E., McCann, L.A., Iwakura, Y., Blinder, Y., Guzik, T.J., Harrison, D.G.
  • Journal Title: Hypertension 55 Pages: 500-507
• [Journal Article] Nucleoprotein diet ameliorates arthritis symptoms in mice transgenic for human T-cell leukemia virus type I (HTLV-I). (2010)
  • Author(s): Ohtaki, H., Yufu, S., Nakamachi, T., Satoh, K., Shimizu, A., Mori, H., Sato, A., Iwakura, Y., Matsunaga, M., Shioda, S.
  • Journal Title: J. Clin. Biochem. Nutr. 46 Pages: 93-104
• [Journal Article] IFN-γis a master regulator of endotoxin shock syndrome in mice primed with heat-killed Propionibacterium acnes. (2010)
  • Author(s): Kawa, K., Tsutsui, H., Uchiyama, R., Kato, J., Matsui, K., Iwakura, Y., Matsumoto, T., Nakanishi, K.
  • Journal Title: Int. Immunol. 22 Pages: 157-166
• [Journal Article] Type I interferon signaling constrains IL-17A/F secretion by gd T cells during bacterial infection. (2010)
  • Author(s): Henry, T., Kirimanjeswara, G.S., Ruby, T., Jones, J.W., Peng, K., Perret, M., Ho, L., Sauer, J. -D., Iwakura, Y., Metzger, D.W., Monack, D.M.
  • Journal Title: J. Immunol. 184 Pages: 3755-67
• [Journal Article] Identification of the cellular sensor that stimulates the inflammatory response to sterile cell death. (2010)
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• [Journal Article] Deficiency of interleukin-1 receptor antagonist induces aortic valve disease in BALB/c mice. (2010)
  • Author(s): Isoda, K., Matsuki, T., Kondo, H., Iwakura, Y., Ohsuzu, F.
  • Journal Title: Arterioscler. Thromb. Vasc. Biol. 30 Pages: 708-15
• [Journal Article] IL-17 contributes to the development of chronic rejection in a murine-heart transpant model. (2010)
  • Author(s): Itoh, S., Nakae, S., Axtell, R.C., Velotta, J.B., Kimura, N., Kajiwara, N., Iwakura, Y., Saito, H., Adachi, H., Steinman, L., Robbins, R.C., Fishbein, M.P.
  • Journal Title: J. Clin. Immunol. 30 Pages: 235-40
• [Journal Article] Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors. (2010)
  • Author(s): Adamopoulos, I.E., Chao, C.C., Geissler, R., Laface, D., Blumenschein, W., Iwakura, Y., McClanahan, T., Bowman, E.P.
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• [Journal Article] IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasis. (2010)
  • Author(s): Teng, M.W.L., Andrews, D.M., McLaughlin, N., von Scheidt, B., Ngiow, S.F., Moller, A., Hill, G.R., Iwakura, Y., Oft, M., Smyth, M.J.
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• [Journal Article] Dectin-2 recognition of α-mannans and induction of Th17 differentiation is essential for host defense against Candida albicans. (2010)
  • Author(s): Saijo, S., Ikeda, S., Yamabe, K., Kakuta, S., Ishigame, H., Akitsu, A., Fujikado, N., Kusaka, T., Kubo, S., Chung, S., Komatsu, R., Miura, N., Adachi, Y., Ohno, N., Shibuya, K., Yamamoto, N., Kawakami, K., Yamasaki, S., Saito, T., Akira, S., Iwakura, Y.
  • Journal Title: Immunity 32 Pages: 1-11
• [Journal Article] IL-17A is dispensable for myocarditis but essential for the progression to dilated cardiomyopathy. (2010)
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• [Journal Article] Th17 cells promote autoimmune anti-myeloperoxidase glomerulomephritits. (2010)
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• [Journal Article] Lung CD4-CD8-double-negative T cells are prominent producers of IL-17A and IFN-gamma during primary respiratory murine infection with Francisella tularensis live vaccine strain. (2010)
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  • Journal Title: J. Immunol. 184 Pages: 5791-5801
• [Journal Article] A Th17-polarized cell population that has infiltrated the lung requires cells that convert to IFN-g production in order to induce airway hyperresponsiveness. (2010)
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• [Journal Article] Activation of myeloid dendritic cells by deoxynucleic acids from Cordyceps sinensis via a Toll-like receptor 9-dependent pathway. (2010)
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  • Journal Title: Cellular Immunol. 263 Pages: 241-250
• [Journal Article] Muramyldipeptide augments the actions of lipopolysacchairde in mice by stimulating macrophages to produe pro-IL-1b and by down-regulation of suppressor of cytokine signaling 1 (SOCS1). (2009)
  • Author(s): Shikama, Y., Kuroishi, T., Nagai, Y., Iwakura, Y., Shimauchi, H., Takada, H., Sugawara, S., Endo, Y.
  • Journal Title: Innate Immun. (Epub ahead of print)
• [Journal Article] CXCL12 promotes CCR7-dependent naive T-cell trafficking to lymph nodes and Peyer's patches. (2009)
  • Author(s): Bai, Z.B., Hayasaka, H., Kobayashi, M., Li, W., Guo, Z., Jang, M. -H., Kondo, A., Choi, B., Iwakura, Y., Miyasaka, M.
  • Journal Title: J. Immunol. 182 Pages: 1287-1295
• [Journal Article] Differential roles of IL-17A and IL-17F in host defense against mucoepithelial bacterial infection and allergic responses. (2009)
  • Author(s): Ishigame, H., Kakuta, S., Nagai, T., Nambu, A., Komiyama, Y., Kadoki, M., Tanahashi, Y., Akitsu, A., Kotaki, H., Sudo, K., Nakae, S., Sasakawa, C., Iwakura, Y.
  • Journal Title: Immunity 30 Pages: 108-119
• [Journal Article] IL-17 promotes progression of cutaneous leishmaniasis in susceptible mice. (2009)
  • Author(s): Lopez Kostka, S., Dinges, S., Griewank, K., Iwakura, Y., Udey, M.C., Von Stebut, E.
  • Journal Title: J. Immunol. 182 Pages: 3039-3046
• [Journal Article] MHC-matched corneal allograft rejection in an IFN-g/IL-17-independent manner in C57BL/6 mice. (2009)
  • Author(s): Yamada, J., Hamuro, J., Fukushima, A., Ohteki, T., Terai, K., Iwakura, Y., Yagita, H., Kinoshita, S.
  • Journal Title: Invest. Ophthalmol. Vis. Sci. 50 Pages: 2139-2146
• [Journal Article] Biotin status affects nickel allergy via regulation of IL-1b production in mice. (2009)
  • Author(s): Kuroishi, T., Kinbara, M., Sato, N., Tanaka, Y., Nagai, Y., Iwakura, Y., Endo, Y., Sugawara, S.
  • Journal Title: J. Nutrition 139 Pages: 1031-1036
• [Journal Article] Host-derived Interleukin-1a is important in determining the immunogenicity of 3-Methylcholantrene-tumor cells. (2009)
  • Author(s): Elkabets, M., Krelin, Y., Dotan, S., Cerwenka, A., Porgador, A., Lichtenstein, R.G., White, M.R., Zoller, M., Iwakura, Y., Dinarello, C.A., Voronov, E., Apte, R.N.
  • Journal Title: J. Immunol. 182 Pages: 4874-4881
• [Journal Article] Virus binding to a plasma membrane receptor triggers interleukin-1α-mediated proinflammatory macrophage response in vivo. (2009)
  • Author(s): Di Paolo, N.C., Miao, E.A., Iwakura, Y., Kaja, M-K., Aderem, A., Flavell, R.A., Papayannopoulou, T., Shayakhmetov, D.M.
  • Journal Title: Immunity 31 Pages: 110-121
• [Journal Article] Toll-like receptor 9-dependent activation of myeloid dendritic cells by deoxynucleic acids from Candida albicans. (2009)
  • Author(s): Miyazato A, Nakamura K, Yamamoto N, Mora-Montes HM, Tanaka M, Abe Y, Tanno D, Inden K, Gang X, Ishii K, Takeda K, Akira S, Saijo S, Iwakura Y, Adachi Y, Ohno N, Mitsutake K, Gow NA, Kaku M, Kawakami K.
  • Journal Title: Infect. Immun. 77 Pages: 3056-3064
• [Journal Article] Hepatic platelet accumulation in Fas-mediated hepatitis in mice. (2009)
  • Author(s): Ohtaki Y, Yamaguchi K, Yu Z, Kumamoto H, Shimauchi H, Iwakura Y, Sugawara S, Endo Y.
  • Journal Title: Int. Immunopharmacol. 9 Pages: 1071-1078
• [Journal Article] A protective function for interleukin 17A in T cell-mediated intestinal inflammation. (2009)
  • Author(s): O'Connor, W. Jr., Kamanaka, M., Booth, C.J., Town, T., Nakae, S., Iwakura, Y., Kolls, J.K., Flavell, R.A.
  • Journal Title: Nat. Immunol. 10 Pages: 603-609
• [Journal Article] IL-17 is involved in bone resorption in mouse periapical lesions. (2009)
  • Author(s): Oseko, F., Yamamoto, T., Akamatsu, Y., Kanamura, N., Iwakura, Y., Imanishi, J., Kita, M.
  • Journal Title: Microbiol. Immunol. 53 Pages: 287-294
• [Journal Article] Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft versus host disease. (2009)
  • Author(s): Yi, T., Chen, Y., Wang, L., Du, G., Huang, D., Zhao, D., Johnstone, H., Young, J., Todorov, I., Umetsu, D.T., Chen, L., Iwakura, Y., Kandeel, F., Forman, S., Zeng, D.
  • Journal Title: Blood 114 Pages: 3101-3112
• [Journal Article] Pulmonary inflammation triggered by Ricin toxin requires macrophages and IL-1 signaling. (2009)
  • Author(s): Lindauer, M.L., Wong, J., Iwakura, Y., Magun, B.E.
  • Journal Title: J. Immunol. 183 Pages: 1419-1426
• [Journal Article] Pivotal role of cerebral interleukin-17-producing gdT cells in the delayed phase of ischemic brain injury. (2009)
  • Author(s): Shichita, T., Sugiyama, Y., Ooboshi, H., Sugimori, H., Nakagawa, R., Takada, I., Iwaki, T., Okada, Y., Iida, M., Cua, D.J., Iwakura, Y., Yoshimura, A.
  • Journal Title: Nat. Med. 15 Pages: 946-950
• [Journal Article] Therapeutic effects of interleukin-6 blockade in a murine model of polymyositis that does not require interleukin-17A. (2009)
  • Author(s): Okiyama, N., Sugihara, T., Iwakura, Y., Yokozeki, H., Miyasaka, N., Kohsaka, H.
  • Journal Title: Arth. Rheum. 60 Pages: 2505-2512
• [Journal Article] Interleukin-1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia. (2009)
  • Author(s): Horino, T., Matsumoto, T., Ishikawa, H., Kimura, S., Uramatsu, M., Tanabe, M., Tateda, K., Miyazaki, S., Aramaki, Y., Iwakura, Y., Yoshida, M., Onodera, S., Yamaguchi, K.
  • Journal Title: Microbiol. Immunol. 53 Pages: 502-511
• [Journal Article] T helper type 17 immune response plays an indispensable role for development of iodine-induced autoimmune thyroiditis in nonobese diabetic-H2h4 mice. (2009)
  • Author(s): Horie, I., Abiru, N., Nagayama, Y., Kuriya, G., Saitoh, O., Ichikawa, T., Iwakura, Y., Eguchi, K.
  • Journal Title: Endocrinology 150 Pages: 5135-5142
• [Journal Article] Interleukin-17 is required for T helper 1 cell immunity and host resistance to the intracellular pathogen Fracisella tularensis. (2009)
  • Author(s): Lin, Y., Ritchea, S., Logar, A., Slight, S., Messmer, M., Rangel-Moreno, J., Guglani, L., Alcorn, J. F., Strawbridge, H., Park, S. M., Onishi, R., Nyugen, N., Walter, M. J., Pociask, D., Randall, T. D., Gaffen, S. L., Iwakura, Y., Kolls, J. K., Khader, S. A*.
  • Journal Title: Immunity 31 Pages: 799-810
• [Journal Article] Natural occurring IL-17 producing T cells regulagte the initial phase of neutrophil mediated airway responses. (2009)
  • Author(s): Tanaka, S., Yoshimoto, T., Naka, T., Nakae, S., Iwakura, Y., Cua, D., Kubo, M.
  • Journal Title: J. Immunol. 183 Pages: 7523-7530
• [Journal Article] Role of T cell TGFβsignaling and IL-17 in allograft acceptance and fibrosis associated with chronic rejection. (2009)
  • Author(s): Faust, S.M., Lu, G., Marini, B.L., Zou, W., Gordon, D., Iwakura, Y., Laouar, Y., Bishop, D.K.
  • Journal Title: J. Immunol. 183 Pages: 7297-7306
• [Journal Article] Tyrosine kinase 2 plays critical roles in the pathogenic CD4 T cell responses for the development of experimental autoimmune encephalomyelitis. (2009)
  • Author(s): Oyamada, A., Ikebem H., Itsumi, M., Saiwai, H., Okada, S., Shimoda, K., Iwakura, Y., Nakayama, K.I., Iwamoto, Y., Yoshikai, Y., Yamada, H.
  • Journal Title: J. Immunol. 183 Pages: 7539-7546
• [Journal Article] Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. (2009)
  • Author(s): Munoz, M., Heimesaat, M. M., Danker, K., Struck, D., Lohmann, U., Plickert, R.,Bereswill, S., Fischer, A., Dunay, I. R., Wolk, K., Loddenkemper, C., Krell, H. -W., Libert, C., Lund, L. R., Frey, O., Holscher, C., Iwakura, Y., Ghilardi, N., Ouyang, W., Kamradt, T., Sabat, R., Liesenfeld, O. Interleukin
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• [Journal Article] IL-1 regulates the Cyp7a1 gene and serum total cholesterol level at steady state in mice. (2008)
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  • Journal Title: Biochem. Biophys. Res. Commun. 379 Pages: 239-242
• [Journal Article] Suppressive role of leukocyte cell-derived chemotaxin 2 in mouse anti-type II collagen antibody-induced arthritis. (2008)
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  • Journal Title: Arthritis Rheum. 58 Pages: 413-421
• [Journal Article] Dcir deficiency causes development of autoimmune diseases in mice due to excess expansion of dendritic cells. (2008)
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• [Journal Article] Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages. (2008)
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• [Journal Article] Differential roles for IFN-g and IL-17 in experimental autoimmune uveoretinitis. (2008)
  • Author(s): Yoshimura, T., Sonoda, K., Miyazaki, Y., Iwakura, Y., Ishibashi, T., Yoshimura, A., Yoshida, H.
  • Journal Title: Int. Immunol. 20 Pages: 209-214
• [Journal Article] Interleukin-1b and macrophage migration inhibitory factor (MIF) in dermal fibroblasts mediate UVA induced matrix metalloproteinase-1 expression. (2008)
  • Author(s): Honda, A., Abe, R., Makino, T., Norisugi, O., Fujita, Y., Watanabe, H., Nishihira, J., Yamagishi, S., Iwakura, Y., Shimizu, H., Shimizu, T.
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• [Journal Article] Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of Natural Killer T cells and IL-17. (2008)
  • Author(s): Pichavant, M., Goya, S., Meyer, E.H., Johnston, R.A., Kim, H.Y., Matangkasombut, P., Zhu, M., Iwakura, Y., Savage, P.B., DeKruyff, R.H., Shore, S.A., Umetsu, D.T.
  • Journal Title: J. Exp. Med. 205 Pages: 385-393
• [Journal Article] Deoxynucleic acids from Cryptococcus neoformans activate myeloid dendritic cells via a TLR9-dependent pathway. (2008)
  • Author(s): Nakamura, K., Miyazato, A., Gang, X., Hatta, M., Inden, K., Aoyagi, T., Takeda, K., Akira, S., Saijo, S., Iwakura, Y., Adachi, Y., Ohno, N., Suzuki, K., Fujita, J., Kaku, M., Kawakami, K.
  • Journal Title: J. Immunol. 180 Pages: 4067-4074
• [Journal Article] IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. (2008)
  • Author(s): Aujla, S.J., Fei, M., Pociask, D.A., Reinhart, T.A., Edeal, J., Gaus, K., Kreindler, J.L., Dubin, P.J., Zheng, M., Pilewski, J.M., Myerburg, M.M., Mason, C.A., Iwakura, Y., Kolls, J.K.
  • Journal Title: Nature Med. 14 Pages: 275-281
• [Journal Article] Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. (2008)
  • Author(s): Luger, D., Silver, P.B., Tang, J., Cua, D., Chen, Z., Iwakura, Y., Bowman, E.P., Sgambellone, N.M., Chan, C. -C., Caspi, R.R.
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• [Journal Article] Endogenous IL-17 does not play a significant role in the development of experimental murine allergic conjunctivitis. (2008)
  • Author(s): Fukushima, A., Sumi, T., Ishida, W., Yamada, J., Iwakura, Y., Ueno, H.
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• [Journal Article] Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. (2008)
  • Author(s): Izcue, A., Hue, S., Buonocore, S., Arancibia-Carcamo, C.V., Ahern, P.P., Iwakura, Y., Maloy, K.J., Powrie, F
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• [Journal Article] L-6-dependent spontaneous proliferation is required for the induction of colitogenic IL-17-producing CD8+ T cells (2008)
  • Author(s): Tajima, M., Wakita, D., Noguchi, D., Chamoto, K., Yue, Z, Fugo, K., Ishigame, H., Iwakura, Y., Kitamura, H., Nishimura, T.
  • Journal Title: J. Exp. Med. 205 Pages: 1019-1027
• [Journal Article] CD44 and Bak expression in IL-6 or TNF-a gene knockout mice after whole lung irradiation. (2008)
  • Author(s): Sakai, M., Iwakawa, M., Iwakura, Y., Ohta, T., Tsujii, H., Imai, T.
  • Journal Title: J. Radiat. Res. 49 Pages: 409-416
• [Journal Article] Development of proteogylcan-induced arthritis is independent of IL-17. (2008)
  • Author(s): Doodes, P.D., Cao, Y., Hamel, K., Wang, Y., Hutas, G., Iwakura, Y., Finnegan, A.
  • Journal Title: J. Immunol. 181 Pages: 329-337
• [Journal Article] CCL2 recruitment of IL-6 producing CD11b+ monocytes to the draining lymph nodes during the initiation of TH17-dependent B cellmediated autoimmunity. (2008)
  • Author(s): Bai, Y, Liu, R., Huang, D., La Cava, A., Tang, Y., Iwakura, Y., Campagnolo, D.I., Vollmer, T.L., Ransohoff, R.M., Shi, F.
  • Journal Title: Eur. J. Immunol. 38 Pages: 1877-1888
• [Journal Article] Host T cells are the main producers of IL-17 within the central nervous system during initiation of experimental autoimmune encephalomyelitis induced by adoptive transfer of Th1 cell lines. (2008)
  • Author(s): Lees, J.R., Iwakura, Y., Russell, J.H.
  • Journal Title: J. Immunol. 180 Pages: 8066-8072
• [Journal Article] Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction. (2008)
  • Author(s): Ogura H., Murakami, M., Okyuyama, Y., Tsuruoka, M., Kitabayashi, C., Kanamoto, M., Nishihara, M., Iwakura, Y., Hirano, T*.
  • Journal Title: Immunity 29 Pages: 628-636
• [Journal Article] IL-17A is produced by Th17 cells, γδ T cells and other CD4- lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearance. (2008)
  • Author(s): Schulz, S.M., Kohler, G., Holscher, C., Iwakura, Y., Alber, G*.
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• [Journal Article] Contribution of IL-1 to resistance to Streptococcus pneumoniae infection. (2008)
  • Author(s): Kafka, D., Ling, E., Feldman, G., Benharroch, D., Voronov, E., Givon-Laci, N., Iwakura, Y., Dagan, R., Apte, R.N., Mizrachi-Nebenzahi, Y.
  • Journal Title: Int. Immunol. 9 Pages: 1139-1146
• [Journal Article] Toll-like receptor 2 (TLR2) and dectin-1 contribute to the production of IL-12p40 by bone marrow-derived dendritic cells infected with Penicillium marneffei. (2008)
  • Author(s): Nakamura, K., Miyazato, A., Koguchi, Y., Adachi, Y., Ohno, N., Saijo, S., Iwakura, Y., Takeda, K., Akira, S., Fujita, J., Ishii, K., Kaku, M., Kawakami, K.
  • Journal Title: Microbes Infect. 10 Pages: 1223-1227
• [Journal Article] IL-17 is Involved in Helicobacter pylori-Induced Gastric Inflammatory Responses in a Mouse Model. (2008)
  • Author(s): Shiomi, S., Toriie, A., Imamura, S., Konishi, H., Mitsufuji, S., Iwkaura, Y., Yamaoka, Y., Ota, H., Yamamoto, T., Imanishi, J., Kita, M.
  • Journal Title: Helicobacter 13 Pages: 518-524
• [Journal Article] The roles of IL-17A in inflammatory immune responses and host defense against pathogens. (2008)
  • Author(s): Iwakura, Y., Nakae, S., Saijo, S., Ishigame, H.
  • Journal Title: Immunological Rev. 226 Pages: 57-79
• [Journal Article] L-17A produced by gammadelta T cells plays a critical role in innate immunity against Listeria monocytogenes infection in the liver. (2008)
  • Author(s): Hamada, S., Umemura, M., Shiono, T., Tanaka, K., Yahagi, A., Begum, M.D., Oshiro, K., Okamoto, Y., Watanabe, H., Kawakami, K., Roark, C., Born, W.K., O'Brien, R., Ikuta, K., Ishikawa, H., Nakae, S., Iwakura, Y., Ohta, T., Matsuzaki, G.
  • Journal Title: J. Immunol. 181 Pages: 3456-3463
• [Journal Article] Involvement of IL-17A in the pathogenesis of DSS-induced colitis in mice. (2008)
  • Author(s): Ito, R., Kita, M., Shin-Ya, M., Kishida, T., Urano, A., Takada, R., Sakagami, J., Imanishi, J., Iwakura, Y., Okanoue, T., Yoshikawa, T., Kataoka, K., Mazda, O.
  • Journal Title: Biochem. Biophys. Res. Commun. 377 Pages: 12-16
• [Journal Article] Deficiency of tumor necrosis factor-a and interferon-g in bone marrow cells synergistically inhibits neointimal formation following vascular injury. (2008)
  • Author(s): Murayama, H., Takahashi, M., Takamoto, M., Shiba, Y., Ise, H., Koyama, J., Tagawa, Y., Iwakura, Y., Ikeda, U.
  • Journal Title: Cardiovascular Res. 80 Pages: 175-180
• [Journal Article] IL-23 and Th17 cells enhance Th2 cell-mediated eosinophilic airway inflammation in mice. (2008)
  • Author(s): Wakashin, H., Hirose, K., Maezawa, Y., Kagami, S., Suto, A., Watanabe, N., Saito, Y., Hatano, M., Tokuhisa, T., Iwakura, Y., Puccetti, P., Iwamoto, I., Nakajima, H.
  • Journal Title: Am. J. Respir. Crit. Care Med. 178 Pages: 1023-1032
• [Journal Article] Human T-cell leukemia virus type I infects human lung epithelial cells and induces gene expression of cytokines, chemokines and cell adhesion molecules. (2008)
  • Author(s): Teruya, H., Tomita, M., Senba, M., Ishikawa, C., Tamayose, M., Miyazato, A., Yara, S., Tanaka, Y., Iwakura, Y., Fujita, J., Mori, N.
  • Journal Title: Retrovirology 5 Pages: 86
• [Journal Article] IL-17 contributes to CD4-mediated graft-versus-host disease. (2008)
  • Author(s): Kappel, L.W., Goldberg, G.L., King, C.G., Suh, D., Smith, O.M., Ligh, C., Holland, A., Grubin, J., Liu, C., Iwakura, Y., Mark, N., Heller, G., van den Brink, M.R.M.
  • Journal Title: Blood 113 Pages: 628-636
• [Journal Article] Protective immunity to systemic infection with Salmonella enterica serovar Enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22 but not IL-17. (2008)
  • Author(s): Schulz, S.M., Kohler, G., Schutze, N., Knauer, J., Straubinger, R.K., Chackerian, A.A., Witte, E., Wolk, K., Sabat, R., Iwakura, Y., Holscher, C., Muller, U., Kastelein, R.A., Alber, G.
  • Journal Title: J. Immunol. 181 Pages: 7891-7901
• [Journal Article] Critical role for mesothelial cells in necrosis-induced inflammation through the recognition of IL-1a released from dying cells. (2008)
  • Author(s): Eigenbrod, T., Park, J-H., Harder, J., Iwakura, Y., Nunez, G.
  • Journal Title: J. Immunol. 181 Pages: 8194-8198
• [Journal Article] IFN-γexpression in CD8+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4+ T cell death. (2008)
  • Author(s): Atsumi, T., Sato, M., Kamimura, D., Moroi, A., Iwakura, Y., Betz, U.A., Yoshimura, A., Nishihara, M., Hirano, T., Murakami, M.
  • Journal Title: Int. Immunol. 21 Pages: 73-80
• [Journal Article] Differential role and tissue specificity of interleukin-1alpha gene expression in atherogenesis and lipid metabolism. (2007)
  • Author(s): Kamari, Y., Werman-Venkert, R., Shaish, A., Werman, A., Harari, A., Gonen, A., Voronov, E., Grosskopf, I., Sharabi, Y., Grossman, E., Iwakura, Y., Dinarello, C.A., Apte, R.N., Harats, D.
  • Journal Title: Atherosclerosis 195 Pages: 31-38
• [Journal Article] Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and cerebellar long-term depression. (2007)
  • Author(s): Kina, S., Tezuka, T., Kusakawa, S., Kishimoto, Y., Kakizawa, S., Hashimoto, K., Ohsugi, M., Kiyama, Y., Horai, R., Sudo, K., Kakuta, S., Iwakura, Y., Iino, M., Kano, M., Manabe, T., Yamamoto, T.
  • Journal Title: Eur. J. Neurosci. 26 Pages: 2269-2278
• [Journal Article] Knockout mice lacking cPGES/p23, a constitutively expressed PGE(2) synthetic enzyme, are peri-natally lethal. (2007)
  • Author(s): Nakatani, Y., Hokonohara, Y., Kakuta, S., Sudo, K., Iwakura, Y., Kudo, I.
  • Journal Title: Biochem. Biophys. Res. Commun. 362 Pages: 387-92
• [Journal Article] Alteration of behavioural phenotype in mice by targeted disruption of the progranulin gene. (2007)
  • Author(s): Kayasuga, Y., Chiba, S., Suzuki, M., Kikusui, T., Matsuwaki, T., Yamanouchi, K., Kotaki, H., Horai, R., Iwakura, Y., Nishihara, M.
  • Journal Title: Behav. Brain Res. 185 Pages: 110-118
• [Journal Article] Anti-type II collagen antibody accelerates arthritis via CXCR2-expressing cells in IL-1 receptor antagonist-deficient mice. (2007)
  • Author(s): Kagari, T., Tanaka, D., Doi, H., Iwakura, Y., Shimozato, T.
  • Journal Title: Eur. J. Immunol. 37 Pages: 2753-2763
• [Journal Article] Melanocortin receptor 2 is required for adrenal gland development, steroidogenesis and neonatal gluconeogenesis. (2007)
  • Author(s): Chida, D., Nakagawa, S., Nagai, S., Sagara, H., Katsumata, H., Imaki, T., Suzuki, H., Mitani, F., Ogishima, T., Shimizu, C., Kotaki, H., Kakuta, S., Sudo, K., Koike, T., Kubo, M., Iwakura, Y.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 18205-18210
• [Journal Article] Blocking of IL-6 signaling pathway prevents CD4+ T cell-mediated colitis in a Th17-independent manner. (2007)
  • Author(s): Noguchi, D., Wakita, D., Tajima, M., Ashino, S., Iwakura, Y., Zhang, Y., Chamoto, K., Kitamura, H., Nishimura, T.
  • Journal Title: Int. Immunol. 19 Pages: 1431-1440
• [Journal Article] Inflammasome-mediated production of IL-1b is required for neutrophil recruitment against Staphylococcus aureus in vivo. (2007)
  • Author(s): Miller, L.S., Pietras, E.M., Uricchio, L.H., Hirano, K., Rao, S., Lin, H., O'Connell, R.M., Iwakura, Y., Cheung, A.L., Cheng, G., Modlin, R.L.
  • Journal Title: J. Immunol. 179 Pages: 6933-6942
• [Journal Article] TNF, but not IL-6 and IL-17, is crucial for the development of T cell-independent psoriasis-like dermatitis in Il1rn-/- mice.
  • Author(s): Nakajima, A., Matsuki, T., Komine, M., Asahina, A., Horai, R., Ishigame, H., Nakae, S., Kakuta, S., Saijo, S., Iwakura, Y.
  • Journal Title: J. Immunol. (in press)
• [Journal Article] The mechanism of lipopolysaccharide-induced human immunodeficiency virus type I activation in transgenic mouse macrophages.
  • Author(s): Kadoki, M., Choi, B.I., Iwakura, Y.
  • Journal Title: Int. Immunol. (in press)
• [Journal Article] Characterization of a variant virus from ascites of subacute granulomatous serositis in interferon-g-deficient C57BL/6 mice persistently infected with murine coronavirus strain JHM.
  • Author(s): Taguchi, F., Matsuyama, S., Iwakura, Y., Tagawa, Y., Saegusa, J., Kyuwa, S.
  • Journal Title: Viral Immunol. (in press)
• [Presentation] The role of DCIR in the development of autoimmune arthritis. (2009)
  • Author(s): Yoichiro Iwakura
  • Organizer: RCAI-JSI International Symposium on Immunology 2009
  • Place of Presentation: Pacifico Yokohama, Yokohama
  • Year and Date: 20090709-20090710
• [Presentation] The Roles of IL-17A and IL-17F in inflammation and host defense against bacteria. Chair man and speaker, Symposium 1: Molecular Basis of Inflammation and Innate Immunity. (2009)
  • Author(s): Yoichiro Iwakura
  • Organizer: The 9th World Congress on Inflammation
  • Place of Presentation: Tokyo, Keio Plaza Hotel, Tokyo
  • Year and Date: 20090706-20090710
• [Presentation] The roles of C-type lectins in the host defense against fungal infection (2009)
  • Author(s): Yoichiro Iwakura
  • Organizer: Keynote Lecture, 17th Congress of the International Society for Human and Animal Mycology (ISHAM 2009)
  • Place of Presentation: Keio Plaza Hotel, Tokyo
  • Year and Date: 20090525-20090529
• [Presentation] 発生工学的アプローチによる創薬ターゲットの探索:関節リウマチをモデルとして (2009)
  • Author(s): 岩倉洋一郎
  • Organizer: 第56回日本実験動物学会シンポジウム「発生工学的アプローチによる創薬ターゲットの探索」(大会長:岩倉洋一郎)
  • Place of Presentation: 大宮ソニックシティー、大宮
  • Year and Date: 20090514-20090516
• [Presentation] マウスモデルが示す関節リウマチの発症機構と治療への道 (2009)
  • Author(s): 岩倉洋一郎
  • Organizer: 第53回日本リウマチ学会賞受賞講演、グランドプリンスホテル新高輪
  • Place of Presentation: 東京
  • Year and Date: 20090423-20090426
• [Presentation] The roles of C-type lectins in the host defense against fungal infection and development of autoimmunity. (2009)
  • Author(s): Yoichiro Iwakura.
  • Organizer: CREST International Symposium: Acquired Immunity and Glycobiology (Organized by Tsubata)
  • Place of Presentation: Kazusa Academia Park, Chiba
  • Year and Date: 20090323-20090324
• [Presentation] 細菌感染防御におけるIL-17A、およびIL-17Fの役割 (2009)
  • Author(s): 岩倉洋一郎
  • Organizer: 第82回日本細菌学会総会シンポジウム「細菌感染と自然免疫」
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 20090312-20090314
• [Presentation] The roles of IL-17A and IL-17F in the immune system. (2009)
  • Author(s): Yoichiro Iwakura
  • Organizer: Th17 Cells in Health and Disease, Keystone Symposium, Fairmont Hotel Vancouver
  • Place of Presentation: British Columbia, Canada
  • Year and Date: 20090205-20090210
• [Presentation] C型レクチン活性化を指標とした機能性食品の開発 (2009)
  • Author(s): 岩倉洋一郎
  • Organizer: Bio Japan 2009アカデミックシーズ発表会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-10-08
• [Presentation] 強直性脊椎炎様関節炎発症におけるC型レクチンの役割 (2009)
  • Author(s): 岩倉洋一郎
  • Organizer: 第98回日本病理学会総会ワークショップ
  • Place of Presentation: 京都国際会館、京都
  • Year and Date: 2009-05-01
• [Presentation] Roles of C-type lectins in immune responses. (2007)
  • Author(s): Yoichiro Iwakura
  • Organizer: BMB2007 (第30回日本分子生物学会、第80回日本生化学会)
  • Place of Presentation: 横浜
  • Year and Date: 20071211-20071215
• [Presentation] Dectin-1の生体防御機構における役割 (2007)
  • Author(s): 西城忍
  • Organizer: 第51回日本医真菌学会総会、ホテルアソシア高山リゾート
  • Place of Presentation: 岐阜
  • Year and Date: 20071109-20071110
• [Presentation] The roles of C-type lectins in the host defense against infection and homeostasis of the immune system. (2007)
  • Author(s): Yoichiro Iwakura
  • Organizer: 第37回日本免疫学会総会・学術集会シンポジウム「Innate immune response and diseases」グランドプリンスホテル新高輪
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Book] nterleukin-1 deficiency and aggressiveness in male mice.(M.T. Czerbnska ed., Psychoneuroendocrinology Research Trends) (2007)
  • Author(s): Tamagawa, A., Kolosova, I., Endo, Y., Gerlinskaya, L., Iwakura, Y., Moshikin, M.
  • Total Pages: 1-16
  • Publisher: Nova Science Publishers, Inc.
• [Book] The roles of IL-17A and IL-17F in mucosal infection and allergy.(ed. S. Jiang, Th17 cells in health and disease)
  • Author(s): Ishigame, H., Nakae, S., Iwakura, Y.
  • Publisher: Springer Science + Buisiness(in press)
• [Remarks] ホームページ等
  • URL: http://www.ims.u-tokyo.ac.jp/cem_dcb/index.html
• [Patent(Industrial Property Rights)] IL-17A/IL-17Fを介した大腸がん発症抑制 (2010)
  • Inventor(s): 岩倉洋一郎、角田茂、鈴木俊佐
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: 61/300962
  • Filing Date: 2010-02-03
  • Acquisition Date: 2010-02-03
• [Patent(Industrial Property Rights)] 骨免疫疾患の予防・治療剤 (2010)
  • Inventor(s): 岩倉洋一郎、藤門範行、馬光宇
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: 2010-37204
  • Filing Date: 2010-02-23
  • Acquisition Date: 2010-02-23
• [Patent(Industrial Property Rights)] IL-17A/IL-17F制御による感染症治療・予防薬Differential Roles of Interleukin-17A and Interleukin-17F in Host Defense against Mucoepithelial Bacterial Infection and Allergic Responses (2009)
  • Inventor(s): 岩倉洋一郎、角田茂、石亀晴道
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: PCT/JP2009/007341
  • Filing Date: 2009-12-28
  • Acquisition Date: 2009-12-28
• [Patent(Industrial Property Rights)] IL-1タイプIIレセプター遺伝子の欠損変異体マウス (2009)
  • Inventor(s): 岩倉洋一郎、角田茂、棚橋侑子、宝来玲子、畦地里衣、中嶋明子
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: PCT/JP2009/051975
  • Filing Date: 2009-02-05
  • Acquisition Date: 2009-02-05
• [Patent(Industrial Property Rights)] IL-17A/IL-17F制御によるアレルギーや細菌感染の治療法の開発Differential Roles of Interleukin-17A and Interleukin-17F in Host Defense against Mucoepithelial Bacterial Infection and Allergic Responses (2008)
  • Inventor(s): 岩倉洋一郎、角田茂、石亀晴道
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: 32878
  • Filing Date: 2008-12-30
  • Acquisition Date: 2008-12-30