QDΖusSf}EX
jC^[tF-γiIFN-γjΉ}EX1) Tagawa, Y., Sekikawa, K., and Iwakura, Y. Suppression of Concanavalin A induced hepatitis in IFN-γ-/-, but not in TNF-α-/-, mice: role for IFN-γ in activating apoptosis of hepatocytes. J. Immunol., 159, 1418-1428 (1997).
2) Yoshimoto, T., Okamura, H., Tagawa, Y., Iwakura, Y., and Nakanishi, K. Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-g production from activated B cells. Proc. Natl. Acad. Sci. USA, 94, 3948-3953 (1997).
3) Sugawara I., Yamada, H., Kazumi, Y., Doi, N., Otomo, K., Aoki, T., Mizuno, S., Udagawa, T., Tagawa, Y., and Iwakura, Y. Induction of granulomas in interferon-g genedisrupted mice by avirulent but not by virulent strains of Mycobacterium tuberuculosis. J. Medical Microbiology, 47, 871-877 (1998).
4) Flamand, V., Donckier, V., Demoor, F. X., Le Moine, A., Matthys, P., Vanderhaeghen, M. L., Tagawa, Y., Iwakura, Y., Billiau, A., Abramowicz, D., and Goldman, M. CD40 ligation prevents neonatal induction of transplantation tolerance. J. Immunol., 160, 4666-4669 (1998).
5) Kyuwa, S., Tagawa, Y., Shibata, S., Doi, K., Machii, K., and Iwakura, Y. Murine coronavirus-induced subacute fatal peritonitis in C57BL/6 mice deficient for interferon-γ. J. Virol., 72, 9286-9290 (1998).
6) Tagawa, Y., Kakuta, S., and Iwakura, Y. Involvement of Fas/Fas ligand system-mediated apoptosis in the development of Concanavalin A-induced hepatitis. Eur. J. Immunol., 28, 4105-4113 (1998).
7) Kyuwa, S., Tagawa, Y., Machii, K., Shibata, S., Doi, K., Fujiwara, K., and Iwakura, Y. MHV-induced fatal peritonitis in mice lacking IFN-γamma. Adv. Exp. Med. Biol. 440, 445-50 (1998).
8) Yano, A., Mun, H.-S., Yang, T.-H., Hata, H., Kobayashi, M., Norose, K., Hayakawa, S., Tagawa, Y., Iwakura, Y., Nakazaki, S., Nakazaki, Y., Sekiya, S., Yamaura, A., Kubosawa, H., Yumoto, N., and Aosai, F. Role of IFN-γ in effector mechanisms and pathogenicity of HSPs in mice and human infected with Toxoplasma gondii. In 9th International Congress of Parasitology, (eds. I. Tada, S. Kojima, and M. Tsuji), Monduzzi Editore, pp. 457-465 (1998).
9) Tsuji, H., Mukaida, N., Harada, A., Kaneko, S., Matsushita, E., Nakanuma, Y., Tsutsui, H., Okamura, H., Nakanishi, K., Tagawa, Y., Iwakura, Y., Kobayashi, K., and Matsushima, K. Alleviation of lipopolysaccharide-induced acute liver injury in Propionibacterium acnes-primed IFN-γ-deficient mice by a concomitant reduction of TNF-α, IL-12 and IL-18 production. J. Immunol., 162, 1049-1055 (1999).
10) Hyodo, Y., Matsui, K., Hayashi, N., Tsutsui, H., Kashiwamura, S., Yamauchi, H., Hiroishi, K., Takeda, K., Akira, S., Tagawa, Y., Iwakura, Y., Kayagaki, N., Yagita, H., Kurimoto, M., Okamura, H., Nakanishi, K., and Higashino, K. Interleukin 18 upregulates perforin-mediated NK activity without increasing perforin mRNA expression by binding to constitutively expressed IL-18R. J. Immunol., 162, 1662-1668 (1999).
11) Sawai, N., Kita, M., Kodama, T., Tanahashi, T., Yamaoka, Y., Tagawa, Y., Iwakura, Y., and Imanishi, J. The role of interferon-γ in Helicobacter pylori-induced gastric inflammatory responses in a mouse model. Infect. Immun., 67, 279-285 (1999).
12) Igarashi, I., Suzuki, R., Waki, S., Tagawa, Y., Seng, S., Tum, S., Omata, Y., Saito, A., Nagasawa, H., Iwakura, Y., Suzuki, N., Mikami, T., and Toyoda, Y. Roles of CD4+ T cells and IFN-γ in protective immunity against Babesia microti infection in mice. Infect. Immun., 67, 4143-4148 (1999).
13) He, J., Ichimura, H., Iida, T., Minami, M., Kobayashi, K., Kita, M., Sotozono, C., Tagawa, Y., Iwakura, Y., and Imanishi, J. Kinetics of cytokine production in the cornea and trigeminal ganglion of C57BL/6 mice after corneal HSV-1 infection. J. Interferon Cytokine Res. 19, 609-615 (1999).
14) Kobayashi, M., Aosai, F., Hata, H., Hye-Seong, M., Tagawa, Y., Iwakura, Y., and Yano. A. Toxoplasma gondii: Difference of invasion into tissue of digestive organs between susceptible and resistant strain and influence of IFN-γ in mice inoculated with the cyst per orally. J. Parasitology, 85, 973-975 (1999).
15) Takikawa, O., Tagawa, Y., Iwakura, Y., Yoshida, R., Truscott, R. J. Interferon-gamma-dependent/independent expression of indoleamine 2,3-dioxygenase. Studies with interferon-gamma-knockout mice. Adv. Exp. Med. Biol., 467, 553-557 (1999).
16) Hino, A., Igarashi, O., Tagawa, Y., Iwakura, Y., and Nariuchi, H. Interferon-g priming is not critical for IL-12 production of murine spleen cells. Cytokine, 12, 12-20 (2000).
17) Tagawa, Y., Matthys, P., Heremans, H., Dillen, C., Zaman, Z., Iwakura, Y., and Billiau, A. Bimodal role of endogenous interleukin-6 in concanavalin A-induced hepatitis in mice. J. Leukocyte Biology, 67, 90-96 (2000).
18) Nishihori, H., Tsuji, H., Wang, H., Tahara, H., Akiyama, M., Ogawa, Y., Matsushima, K., Iwakura, Y., and Mukaida, N. Participation of endogenously produced IFN-γ in interleukin 4-mediated tumor rejection. Human Gene Therapy, 11, 659-668 (2000).
19) Ohkusu, K., Yoshimoto, T., Takeda, K., Ogura, T., Kashiwamura, S., Iwakura, Y., Akira, S., Okamura, H., and Nakanishi, K. Potentiality of interleukin-18 as a useful reagent for treatment and prevention of Leishmania major infection. Infect. Immun., 68, 2449-2456 (2000).
20) Sasaki, S., Nishikawa, S., Miura, T., Mizuki, M., Yamada, K., Madarame, H., Tagawa, Y., Iwakura, Y., and Nakane, A. Interleukin-4 and interleukin-10 are involved in host resistance to Staphylococcus aureus infection through regulation of gamma interferon. Infect. Immun., 68, 2424-2430 (2000).
21) Ohta, A., Sekimoto, M., Sato, M., Koda, T., Nishimura, Si., Iwakura, Y., Sekikawa, K., and Nishimura, T. Indispensable role for TNF-alpha and IFN-γamma at the effector phase of liver injury mediated by Th1 cells specific to hepatitis B virus surface antigen. J. Immunol., 165, 956-961 (2000).
22) Kawakami, K., Koguchi, Y., Qureshi, M. H., Miyazato, A., Yara, S., Kinjo, Y., Iwakura, Y., Takeda, K., Akira, S., Kurimoto, M., and Saito, A. IL-18 contributes to host resistance against infection with Cryptococcus neoformans in mice with defective IL-12 synthesis through induction of IFN-γamma production by NK Cells. J. Immunol., 165, 941-947 (2000).
23) Tanaka, J., Ozaki, H., Yasuda, J., Horai, R., Tagawa, Y., Asano, M., Saijo, S., Imai, M., Sekikawa, K., Kopf, M., and Iwakura, Y. Lipopolysaccharide-induced HIV-I expression in transgenic mice is mediated by tumor necrosis factor-a and interleukin-1, but not by interferon-g nor interleukin-6. AIDS, 14, 1299-1307 (2000).
24) Miura, T., Nishikawa, S., Sasaki, S., Yamada, K., Hasegawa, S., Mizuki, D., Mizuki, M., Hatayama, I., Sekikawa, K., Tagawa, Y., Iwakura, Y., and Nakane, A. Roles of endogenous cytokines in liver apoptosis of mice in lethal Listeria monocytogenes infection. FEMS Immunol. Med. Microbiol., 28, 335-41 (2000).
25) Igarashi, I., Asaba, U., Xuan, X., Omata, Y., Saito, A., Nagasawa, H., Fujisaki, K., Suzuki, N., Iwakura, Y., and Mikami, T. Immunization with recombinant surface antigens p26 with Freund's adjuvants against Babesia rodhaini infection. J. Vet. Med. Sci. 62, 717-723 (2000).
26) Mun, H.-S., Aosai, F., Norose, K., Chen, M., Hata, H., Tagawa, Y., Iwakura, Y., Byun, D.-S., and Yano, A. Toxoplasma gondii Hsp70 as a danger signal in Toxoplasma gondii-infected mice. Cell Stress and Chaperones, 5, 328-335 (2000).
27) Takeda, K., Hayakawa, Y., Smyth, M. J., Kayagaki, N., Yamaguchi, N., Kakuta, S., Iwakura, Y., Yagita, H., and Okumura, K. Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nature Medicine, 7, 94-100 (2001).
28) Seino, K., Fukao, K., Muramoto, K., Yanagisawa, K., Takada, Y., Kakuta, S., Iwakura, Y., Van Kaer, L., Takeda, K., Nakayama, T., Taniguchi, M., Bashuda, H., Yagita, H., and Okumura, K. Requirement for NKT cells in the induction of allograft tolerance. Proc. Natl. Acad. U. S. A., 98, 2577-2581 (2001).
29) Norose, K., Mun, H. S., Aosai, F., Chen, M., Hata, H., Tagawa, Y., Iwakura, Y., Yano, A. Organ infectivity of Toxoplasma gondii in interferon-g knockout mice. J. Parasitol., 87, 447-52 (2001).
30) Yoneto, T., Waki, S., Takai, T., Tagawa, Y., Iwakura, Y., Mizuguchi, J., Nariuchi, H., and Yoshimoto, T. @A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infection. J. Immunol. 166, 6236-6241 (2001).
31) Hayakawa, Y., Takeda, K., Yagita, H., Kakuta, S., Iwakura, Y., Van Kaer, L., Saiki, I., and Okumura, K. Critical contribution of IFN-γamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide. Eur J Immunol,. 31, 1720-1727 (2001).
32) Sato, M., Chamoto, K., Tsuji, T., Iwakura, Y., Togashi, Y., Koda, T., and Nishimura, T. Th1 cytokine-conditioned bone marrow-derived dendritic cells can bypass the requirement for Th functions during the generation of CD8(+) CTL. J. Immunol., 167, 3687-3691 (2001).
33) Dal, J. H., Iwatani, Y., Ishida, T., Terunuma, H., Kasai, H., Iwakura, Y., Fujiwara, H., and Ito, M. Glycyrrhizin enhances interleukin-12 production in peritoneal macrophage. Immunology, 103, 235-243 (2001).
34) Miura, T., Kudo, T., Matsuki, A., Sekikawa, K., Tagawa, Y., Iwakura, Y., Nakane, A. Effect of 6-Hydroxydopamine on host resistance against Listeria monocytogenes infection. Infect. Immun., 69, 7234-7241 (2001).
35) Kyuwa, S., Kawamura, S., Shibata, S. Machii, K., Tagawa, Y., Iwakura, Y., and Urano, T. The severity of hepatic lesion after intraperitoneal JHMV infection in IFN-γamma deficient mice is parallel to viral replication in hepatocytes in vitro. Adv Exp Med Biol., 494, 95-99 (2001).
36) Yoshida, K., Matsumoto, T., Tateda, K., Uchida, K., Tsujimoto, S., Iwakura, Y., and Yamaguchi, K. Protection against pulmonary infection with Klebsiella pneumoniae in mice by interferon-gamma through activation of phagocytic cells and stimulation of production of other cytokines. J. Med. Microbiol., 50, 959-964 (2001).
37) Kakuta, S., Tagawa, Y., Shibata, S., Nanno, M., and Iwakura, Y. Inhibition of B16 melanoma experimental metastasis by interferon-g through direct inhibition of cell proliferation and activation of anti-tumor host mechanisms. Immunology, 105, 92-100 (2002).
38) Kyuwa, S., Shibata, S., Tagawa, Y., Iwakura, Y., Machii, K., and Urano, T.@Acute hepatic failure in IFN-γ-deficient BALB/c mice after murine coronavirus infection. Virus Research, 83, 169-77 (2002).
39) Shinozawa, Y., Matsumoto, T., Uchida, K., Tsujimoto, S., Iwakura, Y., and Yamaguchi, K. Role of interferon-gamma in inflammatory responses in murine respiratory infection with Legionella pneumophila. J. Med. Microbiol., 51, 225-230 (2002).
40) Battsetseg, B., Mamiro, K., Inoue, N., Makala, L., Nagasanw, H., Iwakura, Y., Toyoda, Y., Mikami, T., Fujisaki, K. Immune responses of interferon gamma (IFN-γ) knock out mice to repeated Haemaphysalis longicornis (Acari: Ixodidae) nymph infestations. J. Med. Entomol., 39, 173-176 (2002).
41) Ishida, Y., Kondo, T., Ohshima, T., Fujiwara, H., Iwakura, Y., and Mukaida, N. A pivotal involvement of IFN-g in the pathogenesis of acetaminophen-induced acute liver injury. FASEB J., in press.
42) Sasaki, S., Omoe, K., Tagawa, Y., Iwakura, Y., Sekikawa, K., Shinagawa, K., and Nakane, A. Roles of γ interferon and tumor necrosis factor-α in shiga toxin lethality. Microb. Pathog., 33, 43-47 (2002).
43) Konishi, H., Tsutsui, H., Murakami, T., Yumikura-Futatsugi, S., Yamanaka, K., Tanaka, M., Iwakura, Y., Suzuki, N., Fuchs,E. V., Takeda, K., Akira, S., Nakanishi, K., and Mizutani, H. IL-18 contributes to the spontaneous development of atopic dermatitis-like inflammatory skin lesion independently of IgE/stat6 under specific pathogen-free conditions. Proc. Natl. Acad. Sci. USA, 99, 11340-11345 (2002).
44) Minami, M., Kita, M., Yan, X.-Q., Yamamoto, T., Iida, T., Sekikawa, K., Iwakura, Y., and Imanishi, J. Role of IFN-γ and tumor necrosis factor-α in herpes simplex virus type I infection. J. Interferon Cytokine Res., 22, 671-676, (2002).
45) Desaki, M., Sugawara, I., Iwakura, Y., Yamamoto, K. and Takizawa, H. Role of interferon-γ in the development of murine bronchus-associated lymphoid tissues induced by silica in vivo. Toxicol. Appl. Pharmacol., 185, 1-7 (2002).
46) Yano, A., Mun, H.S., Chin, M., Norose, K., Hata, K., Kobayashi, M., Aosai, F. and Iwakura, Y. Roles of IFN-γ on stage conversion of an obligate intracellular protozoan parasite, Toxoplasma gondii. Int. Rev. Immunol., 21, 405-21 (2002).
47) Kyuwa, S., Kawamura, S., Tagawa, Y., Iwakura, Y., Urano, T., and Yoshikawa, Y. Differences between BALB/c and C57BL/6 mice in mouse hepatitis virus replication in primary hepatocyte culture. Exp. Anim., 52, 81-84 (2003).
48) Mun, HS., Aosai, F., Chen, M., Piao, LX., Norose, K., Iwakura, Y., Yano, A. Pathogenicity of Toxoplasma gondii through B-2 cell-mediated downregulation of host defense responses. Microbiol Immunol., 47, 533-542 (2003).
49) Kariyone, A., Tamura, T., Kano, H., Iwakura, Y., Takeda, K., Akira, S., and Takatsu, K. Immunogenicity of Peptide-25 of Ag85B in Th1 development: role of IFN-γ. Int. Immunol., 15, 1183-1194 (2003).
50) Norose, K., Mun, H.S., Aosai, F., Chen, M., Piao, L.X., Kobayashi, M., Iwakura, Y., and Yano, A. IFN-γ-Regulated Toxoplasma gondii Distribution and Load in the Murine Eye. Invest. Ophthalmol. Vis. Sci., 44, 4375-4381 (2003).
51) Ishida Y, Kondo T, Takayasu T, Iwakura Y, Mukaida N. The Essential Involvement of Cross-Talk between IFN-γ and TGF-ΐ in the Skin Wound-Healing Process. J. Immunol., 172, 1848-1855 (2004).
52) Ishida, Y., Maegawa, T., Konodo, T., Kimura, A., Iwakura, Y., Nakamura, S., Mukaida, N. Essential Involvement of IFN-γ in Clostridium difficile Toxin A-induced Enteritis. J. Immunol., 172, 3018-3025 (2004).
53) Belal, U.S., Norose, K., Aosai, F., Mun, H.S., Ahmed, A.K., Chen, M., Mohamed, R.M., Piao, L.X., Iwakura, Y., and Yano, A. Evaluation of the Effects of Sulfamethoxazole on Toxoplasma gondii Loads and Stage Conversion in IFN-γ Knockout Mice Using QC-PCR. Microbiol. Immunol., 48, 185-193 (2004).
54) Kawakami, K., Kinjo, Y., Uezu, K., Miyagi, K., Kinjo, T., Yara, S., Koguchi, Y., Miyazato, A., Shibuya, K., Iwakura, Y., Takeda, K., Akira, S., and Saito, A. Interferon-γ production and host protective response against Mycobacterium tuberculosis in mice lacking both IL-12p40 and IL-18. Microbes. Infect., 6, 339-349 (2004).
55) Yoshimoto, T., Okada, K., Morishima, N., Kamiya, S., Owaki, T., Asakawa, M., Iwakura, Y., Fukai, F., and Mizuguchi, J. Induction of IgG2a Class Switching in B Cells by IL-27. J. Immunol., 173, 2479-2485 (2004).
56) Kudo, M., Aosai, F., Mun, H.S., Norose, K., Akira, S., Iwakura, Y., and Yano, A. The Role of IFN-γ and Toll-Like Receptors in Nephropathy Induced by Toxoplasma gondii Infection. Microbiol. Immunol., 48, 617-628 (2004).
57) Hasegawa, S., Nishikawa, S., Miura, T., Saito, Y., Madarame, H., Sekikawa, K., Tagawa, Y., Iwakura, Y., and Nakane, A. Tumor necrosis factor-α is required for gastritis induced by Helicobacter felis infection in mice. Microb. Pathog., 37, 119-124 (2004).
58) Yamamoto, T., Kita, M., Ohno, T., Iwakura, Y., Sekikawa, K., and Imanishi, J. Role of Tumor Necrosis Factor-α and Interferon-γ in Helicobacter pylori Infection. Microbiol. Immunol., 48, 647-654 (2004).
59) Sakuraba, H., Ishiguro, Y., Yamagata, K., Tagawa, Y., Iwakura, Y., Sekikawa, K., Munakata, A., and Nakane, A. Transforming Growth Factor-ΐ Regulates Susceptibility of Epithelial Apoptosis in Murine Model of Colitis. Ann. N. Y. Acad. Sci., 1029, 382-384 (2004).
60) Wakabayashi, T., Hu, D.L., Tagawa, Y., Sekikawa, K., Iwakura, Y., Hanada, K., and Nakane, A. IFN-γ and TNF-α are involved in urushiol-induced contact hypersensitivity in mice. Immunol. Cell Biol., 83, 18-24 (2005).
61) Sasaki, S., Tagawa, Y., Iwakura, Y., and Nakane, A. The role of gamma interferon in aquired host resistance against Staphylococcus aureus infection in mice. FEMS Immunol. Med. Microbiol., 46, 367-374 (2006).
62) Shimizu, M., Shimamura, M., Owaki, T., Asakawa, M., Fujita, K., Kudo, M., Iwakura, Y., Takeda, Y., Mizuguchi, J., and Yoshimoto, T. Antiangiogenic and antitumor activities of IL-27. J. Immunol., 176, 7317-7324 (2006).
63) Ito, R., Shin-Ya, M., Kishida, T., Urano, A., Takeda, R., Sakagami, J., Imanisho, J., Kita, M., Ueda, Y., Iwakura, Y., Kataoka, K., Okanoue, T., and Mazda, O. Interferon-γ is causatively involved in experimental inflammatory bowel disease in mice. Clin. Exp. Immunol., 146, 330-338 (2006).
64) Nakamatsu, M., Yamamoto, N., Hatta, M., Nakasone, C., Kinjo, T., Miyagi, K., Uezu, K., Nakamura, K., Nakayama, T., Taniguchi, M., Iwakura, Y., Kaku, M., Fujita, J., and Kawakami, K. Role of interferon-γ in Vα14+ natural killer T cell-mediated host defense against Streptococcus pneumoniae infection in murine lungs. Microbes Infect., 9, 364-374 (2007).
65) Togashi, Y., Chamoto, K., Wakita, D., Tsutsumi, N., Iwakura, Y., Matsubara, N., Kitamura, H., and Nishimura, T. Natural killer T cells from interleukin-4-deficient mice are defective in early interferon-γ production in response to α-galactosylceramide. Cancer Sci., 98, 721-725 (2007).
66) Hayashi, T., Ishida, Y., Kimura, A., Iwakura, Y., Mukaida, N., and Kondo, T. IFN-γ Protects Cerulein-Induced Acute Pancreatitis by Repressing NF-ΘB Activation. J. Immunol., 178, 7385-7394 (2007).
67) Kaiga, T., Sato, M., Kaneda, H., Iwakura, Y., Takayama, T., and Tahara, H. Systemic Administration of IL-23 Induces Potent Antitumor Immunity Primarily Mediated through Th1-Type Response in Association with the Endogenously Expressed IL-12. J. Immunol., 178, 7571-7580 (2007).
68) Kohyama, K., Ohno, S., Isoda, A., Moriya, O., Belladonna, ML., Hayashi, H., Iwakura, Y., Yoshimoto, T., Akatsuka, T., and Matsui, M. IL-23 Enhances Host Defense against Vaccinia Virus Infection Via a Mechanism Partly Involving IL-17. J. Immunol., 179, 3917-3925 (2007).
69) Murayama, H., Takahashi, M., Takamoto, M., Shiba, Y., Ise, H., Koyama, J., Tagawa, Y.I., Iwakura, Y., and Ikeda, U. Deficiency of Tumor Necrosis Factor-α and Interferon-γ in Bone Marrow Cells Synergistically Inhibits Neointimal Formation Following Vascular Injury. Cardiovasc. Res., 80, 175-180 (2008).
70) Atsumi, T., Sato, M., Kamimura, D., Moroi, A., Iwakura, Y., Betz, U.A., Yoshimura, A., Nishihara, M., Hirano, T., and Murakami, M. IFN-γ expression in CD8+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4+ T cell death. Int. Immunol., 21, 73-80 (2009).
71) Oseko, F., Yamamoto, T., Akamatsu, Y., Kanamura, N., Iwakura, Y., Imanishi, J., and Kita, M. IL-17 is involved in bone resorption in mouse periapical lesions. Microbiol. Immunol., 53, 287-294 (2009).
72) Kawa, K., Tsutsui, H., Uchiyama, R., Kato, J., Matsui, K., Iwakura, Y., Matsumoto, T., and Nakanishi, K. IFN-γ is a master regulator of endotoxin shock syndrome in mice primed with heat-killed Propionibacterium acnes. Int. Immunol., 22, 157-166 (2010).
73) Henry, T., Kirimanjeswara, G.S., Ruby, T., Jones, J.W., Peng, K., Perret, M., Ho, L., Sauer, J.D., Iwakura, Y., Metzger, D.W., and Monack, D.M. Type I IFN Signaling Constrains IL-17A/F Secretion by γΒT cells during Bacterial Infections. J. Immunol., 184, 3755-3767 (2010).
74) Okamoto Yoshida, Y., Umemura, M., Yahagi, A., O'Brien, R.L., Ikuta, K., Kishihara, K., Hara, H., Nakae, S., Iwakura, Y., and Matsuzaki, G. Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung. J. Immunol., 184, 4414-4422 (2010).
75) Kyuwa, S., Takagaki, S., Matsuyama, S., Taguchi, F., Saegusa, J., Iwakura, Y., Tagawa, Y., and Yoshikawa, Y. Characterization of a Variant Virus from Ascitic Fluid of Subacute Granulomatous Serositis in Interferon-gamma-Deficient C57BL/6 Mice Persistently Infected with Murine Coronavirus Strain JHM. Viral Immunol., 23, 437-442 (2010).
jIL-1Ή}EX
@@IL-1αAIL-1ΐAIL-1α/ΐ
1) Horai, R., Asano, M., Sudo, K., Kanuka, H., Suzuki, M., Nishihara, M., Takahashi, M., and Iwakura, Y. Production of mice deficient in genes for IL-1a, IL-1b, IL-1a/b, and IL-1 receptor antagonist shows that IL-1b is crucial in turpentine-induced fever development and glucocorticoid secretion. J. Exp. Med., 187, 1463-1475 (1998).
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50) Deng, X., Yu, Z., Funayama, H., Shoji, N., Sasano, T., Iwakura, Y., Sugawara, S., and Endo, Y. Mutual augmentation of the induction of the histamine-forming enzyme, histidine decarboxylase, between alendronate and immuno-stimulants (IL-1, TNF, and LPS), and its prevention by clodronate. Toxicol. Appl. Pharmacol., 213, 64-73 (2006).
51) Tateno, K., Minamino, T., Toko, H., Akazawa, H., Shimizu, N., Takeda, S., Kunieda, T., Miyauchi, H., Oyama, T., Matsuura, K., Nishi, JI., Kobayashi, Y., Nagai, T., Kuwabara, Y., Iwakura, Y., Nomura, F., Saito, Y., and Komuro, I. Critical Roles of Muscle-Secreted Angiogenic Factors in Therapeutic Neovascularization. Circ. Res., 98, 1194-1202 (2006).
52) Voronov, E., Dayan, M., Zinger, H., Gayvoronsky, L., Lin, JP., Iwakura, Y., Apte, RN., and Mozes, E. IL-1ΐ-deficient mice are resistant to induction of experimental SLE. Eur. Cytokine Netw., 17, 109-116 (2006).
53) Furuichi, K., Wada, T., Iwata, Y., Kokubo, S., Hara, A., Yamahana, J., Sugaya, T., Iwakura, Y., Matsushima, K., Asano, M., Yokoyama, H., and Kaneko, S. Interleukin-1-dependent sequential chemokine expression and inflammatory cell infiltration in ischemia-reperfusion injury. Crit. Care Med., 34, 2447-2455 (2006).
54) Maedler, K., Schumann, DM., Sauter, N., Ellingsgaard, H., Bosco, D., Baertschiger, R., Iwakura, Y., Oberholzer, J., Wollheim, CB., Gauthier, BR., Donath, MY. Low Concentration of Interleukin-1ΐ Induces FLICE-Inhibitory Protein-Mediated ΐ-Cell Proliferation in Human Pancreatic Islets. Diabetes, 55, 2713-2722 (2006).
55) Krelin, Y., Voronov, E., Dotan, S., Elkabets, M., Reich, E., Fogel, M., Huszar, M., Iwakura, Y., Segal, S., Dinarello, CA., and Apte, RN. Interleukin-1ΐ-Driven Inflammation Promotes the Development and Invasiveness of Chemical Carcinogen-Induced Tumors. Cancer Res., 67, 1062-1071 (2007).
56) Nigrovic, PA., Binstadt, BA., Monach, PA., Johnsen, A., Gurish, M., Iwakura, Y., Benoist, C., Mathis, D., and Lee, DM. Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. Proc. Natl. Acad. Sci. USA., 104, 2325-2330 (2007).
57) Sugihara T, Sekine C, Nakae T, Kohyama K, Harigai M, Iwakura Y, Matsumoto Y, Miyasaka N, Kohsaka H. A new murine model to define the critical pathologic and therapeutic mediators of polymyositis. Arthritis Rheum., 56, 1304-1314 (2007).
58) Sato, N., Kinbara, M., Kuroishi, T., Kimura, K., Iwakura, Y., Ohtsu, H., Sugawara, S., and Endo, Y. Lipopolysaccharide promotes and augments metal allergies in mice, dependent on innate immunity and histidine decarboxylase. Clin Exp Allergy. 37, 743-751 (2007).
59) Ohama, T., Hori, M., Momotani, E., Iwakura, Y., Guo, F., Kishi, H., Kobayashi, S., and Ozaki, H. Intestinal inflammation down-regulates smooth muscle CPI-17 through induction of TNF-α and causes motility disorders. Am. J. Physiol. Gastrointest. Liver Physiol., 292, G1429-1438 (2007).
60) Takagi, K., Matsumura, S., Okuda-Ashitaka, E., Okuda, K., Watanabe, J., Takahashi, H., Iwakura, Y., and Ito, S. Interleukin-1 is not essential for expression of inducible NOS in hepatocytes induced by lipopolysaccharide in vivo. Nitric Oxide, 16, 433-441 (2007).
61) Tamagawa, A., Kolosova, I., Endo, Y., Gerlinskaya, L., Iwakura, Y., and Moshikin, M.? Interleukin-1 deficiency and aggressiveness in male mice.?? In gPsychoneuroendocrinology Research Trendsh, M. T. Czerbnska ed., Nova Science Publishers, Inc., pp1-16 (2007).
62) Kamari, Y., Werman-Venkert, R., Shaish, A., Werman, A., Harari, A., Gonen, A., Voronov, E., Grosskopf, I., Sharabi, Y., Grossman, E., Iwakura, Y., Dinarello, CA., Apte, RN., and Harats, D. Differential role and tissue specificity of interleukin-1α gene expression in atherogenesis and lipid metabolism. Atherosclerosis, 195, 31-38 (2007).
63) Miller, LS., Pietras, EM., Uricchio, LH., Hirano, K., Rao, S., Lin, H., O'Connell, RM., Iwakura, Y., Cheung, AL., Cheng, G., and Modlin, RL. Inflammasome-Mediated Production of IL-1 Is Required for Neutrophil Recruitment against Staphylococcus aureus In Vivo. J. Immunol., 179, 6933-6942 (2007).
64) Chida, D., and Iwakura, Y.? Peripheral TNFα, but not peripheral IL-1, requires endogenous IL-1 or TNFα induction in the brain for the febrile response.? Biochem. Biophys. Res. Commun., 364, 765-770 (2007).
65) Honda, A., Abe, R., Makino, T., Norisugi, O., Fujita, Y., Watanabe, H., Nishihira, J., Iwakura, Y., Yamagishi, SI., Shimizu, H., and Shimizu, T. Interleukin-1ΐ and macrophage migration inhibitory factor (MIF) in dermal fibroblasts mediate UVA-induced matrix metalloproteinase-1 expression. J. Dermatol. Sci., 49, 63-72 (2008).
66) Kafka, D., Ling, E., Feldman, G., Benharroch, D., Voronov, E., Givon-Lavi, N., Iwakura, Y., Dagan, R., Apte, R.N., and Mizrachi-Nebenzahl, Y. Contribution of IL-1 to resistance to Streptococcus pneumoniae infection. Int. Immunol., 20, 1139-1146 (2008).
67) Eigenbrod, T., Park, J.H., Harder, J., Iwakura, Y., and Nunez G. Critical Role for Mesothelial Cells in Necrosis-Induced Inflammation through the Recognition of IL-1α Released from Dying Cells. J. Immunol., 181, 8194-8198 (2008).
68) Kojima, M., Ashino, T., Yoshida, T., Iwakura, Y., Sekimoto, M., and Degawa, M. IL-1 regulates the Cyp7a1 gene and serum total cholesterol level at steady state in mice. Biochem. Biophys. Res. Commun., 379, 239-242 (2009).
69) 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., and Apte, R.N. Host-derived interleukin-1α is important in determining the immunogenicity of 3-methylcholantrene tumor cells. J. Immunol., 182, 4874-4881 (2009).
70) Kuroishi, T., Kinbara, M., Sato, N., Tanaka, Y., Nagai, Y., Iwakura, Y., Endo, Y., and Sugawara, S. Biotin Status Affects Nickel Allergy via Regulation of Interleukin-1ΐ Production in Mice. J. Nutr., 139, 1031-1036 (2009)
71) Ohtaki, Y., Yamaguchi, K., Yu, Z., Kumamoto, H., Shimauchi, H., Iwakura, Y., Sugawara, S., and Endo, Y. Hepatic platelet accumulation in Fas-mediated hepatitis in mice. Int. Immunopharmacol., 9, 1071-1078 (2009).
72) Lindauer, M.L., Wong, J., Iwakura, Y., and Magun, B.E. Pulmonary Inflammation Triggered by Ricin Toxin Requires Macrophages and IL-1 Signaling. J. Immunol., 183, 1419-1426 (2009).
73) Di Paolo, N.C., Miao, E.A., Iwakura, Y., Murali-Krishna, K., Aderem, A., Flavell, R.A., Papayannopoulou, T., Shayakhmetov, D.M. Virus Binding to a Plasma Membrane Receptor Triggers Interleukin-1α-Mediated Proinflammatory Macrophage Response In Vivo. Immunity, 31, 110-121 (2009).
74) Honore, P., Donnelly-Roberts, D., Namovic, M., Zhong, C., Wade, C., Chandran, P., Zhu, C., Carroll, W., Perez-Medrano, A., Iwakura, Y., and Jarvis, M.F. The Antihyperalgesic Activity of a Selective P2X7 Receptor Antagonist, A-839977, is Lost in IL-1αΐ Knockout Mice. Behav. Brain Res., 204, 77-81 (2009).
75) Horino, T., Matsumoto, T., Ishikawa, H., Kimura, S., Uramatsu, M., Tanabe, M., Tateda, K., Miyazaki, S., Aramaki, Y., Iwakura, Y., Yoshida, M., Onodera, S., and Yamaguchi, K. Interleukin-1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia. Microbiol. Immunol., 53, 502-511 (2009).
76) Kono, H., Karmarkar, D., Iwakura, Y., and Rock, K.L. Identification of the Cellular Sensor That Stimulates the Inflammatory Response to Sterile Cell Death. J. Immunol., 184, 4470-4478 (2010).
77) Chou, R.C., Kim, N.D., Sadik, C.D., Seung, E., Lan, Y., Byrne, M.H., Haribabu, B., Iwakura, Y., and Luster, A.D. Lipid-Cytokine-Chemokine Cascade Drives Neutrophil Recruitment in a Murine Model of Inflammatory Arthritis. Immunity, 33, 266-278 (2010).
78) St Pierre, C.A., Chan, M., Iwakura, Y., Ayers, D.C., Kurt-Jones, E.A., and Finberg, R.W. Periprosthetic osteolysis: Characterizing the innate immune response to titanium wear-particles. J. Orthop. Res., 28, 1418-1424 (2010).
80) Kautz-Neu, K., Kostka, S.L., Dinges, S., Iwakura, Y., Udey, M.C., and Von Stebut, E. IL-1 signalling is dispensable for protective immunity in Leishmania-resistant mice. Exp. Dermatol., 20, 76-78 (2011).
81) Shikama, Y., Kuroishi, T., Nagai, Y., Iwakura, Y., Shimauchi, H., Takada, H., Sugawara, S., and Endo, Y. Muramyldipeptide augments the actions of lipopolysaccharide in mice by stimulating macrophages to produce pro-IL-1B and by down-regulation of suppressor of cytokine signaling 1 (SOCS1). Innate Immun. 17, 3-15 (2011).
82) Tanaka, S., Kondo, H., Kanda, K., Ashino, T., Nakamachi, T., Sekikawa, K., Iwakura, Y., Shioda, S., Numazawa, S., and Yoshida, T. Involvement of interleukin-1 in lipopolysaccaride-induced microglial activation and learning and memory deficits. J. Neurosci. Res., 89, 506-514 (2011).
83) Cho, J.S., Zussman, J., Donegan, N.P., Ramos, R.I., Garcia, N.C., Uslan, D.Z., Iwakura, Y., Simon, S.I., Cheung, A.L., Modlin, R.L., Kim, J., and Miller, L.S. Noninvasive In Vivo Imaging to Evaluate Immune Responses and Antimicrobial Therapy against Staphylococcus aureus and USA300 MRSA Skin Infections. J. Invest. Dermatol., 131, 907-915 (2011).
j|Ig Zv^[Ή}EX
1) Shimada, S., Kawaguchi-Miyashita, M., Kushiro, A., Sato, T., Nanno, M., Sako, T., Matsuoka, Y., Sudo, K., Tagawa, Y., Iwakura, Y., and Ohwaki, M. Generation of polymeric immunoglobulin receptor-deficient mouse with marked reduction of secretory IgA. J. Immunol. 163, 5367-5373 (1999).
2) Asahi, Y., Shimada, S., Watanabe, I., Yoshikawa, T., Sato, Y., Iwasaki, T., Hasegawa, H., Ohwaki, M., Iwakura, Y., Suzuki, Y., Aizawa, C., Sata, T., Kurata, T., and Tamura, S. Protection against influenza virus infection in poly Ig receptor-knockout mice immunized intranasally with adjuvant-combined vaccines. J. Immunol., 168, 2930-2938 (2002).
3) Asahi-Ozaki, Y., Yoshikawa, T., Iwakura, Y., Suzuki, Y., Tamura, S., Kurata, T., and Sata, T. Secretory IgA antibodies provide cross-protection against infection with different strains of influenza B virus. J. Med. Virol., 74, 328-335 (2004).
jAML-1 dominant negativeΜgXWFjbN}EX
1) Hayashi, K., Natsume, W., Watanabe, T., Abe, N., Iwai, N., Okada, H., Ito, Y., Asano, M., Iwakura, Y., Habu, S., Takehama, Y., and Satake, M. Diminution of the AML1 transcription factor function causes differential effects on the fates of CD4 and CD8 single positive T cells. J. Immunol., 165, 6816-6824 (2000).
jMD-1Ή}EX
1) Nagai Y, Shimazu R, Ogata H, Akashi S, Sudo K, Yamasaki H, Hayashi S, Iwakura Y, Kimoto M, Miyake K. Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide. Blood. 99,1699-705 (2002).
jMD-2Ή}EX
1) Nagai, Y., Akashi, S., Nagafuku, M., Ogata, M., Iwakura, Y., Akira, S., Kitamura, T., Kosugi, A., Kimoto, M., and Miyake, K. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat. Immunol., 3, 667-672 (2002).
jIL-17Ή}EX
@@IL-17AAIL-17FAIL-17AF
1) Nakae, S., Komiyama, Y., Nambu, A., Sudo, K., Iwase, M., Homma, I., Sekikawa, K., Asano, M., and Iwakura, Y. Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, resulting in the suppression of allergic cellular and humoral responses. Immunity, 17, 375-387 (2002).
2) Nakae, S., Saijo, S., Horai, R., Sudo, K., Mori, S., and Iwakura, Y. IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist. Proc. Natl. Acad. Sci. USA, 100, 5986-5990 (2003).
3) Nakae, S., Nambu, A., Sudo, K., and Iwakura, Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J. Immunol., 171, 6173-6177 (2003).
4) Ishigame, H., Nakajima, A., Saijo, S., Komiyama, Y., Matsuki, T., Nakae, S., Horai, R., Kakuta, S., and Iwakura, Y. The role of TNFα and IL-17 in the development of excess IL-1 signaling-induced inflammatory diseases in IL-1 receptor antagonist-deficient mice. In "Cytokines as Potential Therapeutic Targets for Inflammatory Skin Disease", (eds. Numerof, R., Dinarello, C.A., and Asadullah, K.), Ernst Schering Research Foundation Workshop 56, pp.129-153, (2006).
5) Iwakura, Y., and Ishigame, H. The IL-23/IL-17 axis in inflammation. J. Clin. Invest., 116, 1218-1222 (2006).
6) Komiyama, Y., Nakae, S., Matsuki, T., Nambu, A., Ishigame, H., Kakuta, S., Sudo, K., and Iwakura, Y. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J. Immunol., 177, 566-573 (2006).
7) Sato, K., Suematsu, A., Okamoto, K., Yamaguchi, A., Morishita, Y., Kadono, Y., Tanaka, S., Kodama, T., Shizuo, A., Iwakura, Y., Cua, D.J., and Takayanagi, H. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J. Exp. Med., 203, 2673-2682 (2006).
8) Hirota, K., Hashimoto, M., Yoshitomi, H., Tanaka, S., Nomura, T., Yamaguchi, T., Iwakura, Y., Sakaguchi, N., and Sakaguchi, S. T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J. Exp. Med., 204, 41-47 (2007).
9) Umemura, M., Yahagi, A., Hamada, S., Begum, MD., Watanabe, H., Kawakami, K., Suda, T., Sudo, K., Nakae, S., Iwakura, Y., and Matsuzaki, G. IL-17-Mediated Regulation of Innate and Acquired Immune Response against Pulmonary Mycobacterium bovis Bacille Calmette-Guerin Infection. J. Immunol., 178, 3786-3796 (2007).
10) Numasaki, M., Tagawa, M., Hidaka, M., Suzuki, T., Nakamura, A., Okada, M., Iwakura, Y., Aiba, S., and Yamaya, M. IL-28 Elicits Antitumor Responses against Murine Fibrosarcoma. J. Immunol., 178, 5086-5098 (2007).
11) Nakae, S., Iwakura, Y., Suto, H., and Galli, SJ. Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17. J. Leukoc. Biol., 81, 1258-1268 (2007).
12) Kohyama, K., Ohno, S., Isoda, A., Moriya, O., Belladonna, ML., Hayashi, H., Iwakura, Y., Yoshimoto, T., Akatsuka, T., and Matsui, M. IL-23 Enhances Host Defense against Vaccinia Virus Infection Via a Mechanism Partly Involving IL-17. J. Immunol., 179, 3917-3925 (2007).
13) Noguchi, D., Wakita, D., Tajima, M., Ashino, S., Iwakura, Y., Zhang, Y., Chamoto, K., Kitamura, H., and Nishimura, T. Blocking of IL-6 signaling pathway prevents CD4+ T cell-mediated colitis in a Th17-independent manner. Int Immunol., 19, 1431-1440 (2007).
14) Yoshimura, T., Sonoda, KH., Miyazaki, Y., Iwakura, Y., Ishibashi, T., Yoshimura, A., and Yoshida, H. Differential roles for IFN-γ and IL-17 in experimental autoimmune uveoretinitis. Int. Immunol., 20, 209-214 (2008).
15) 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., and Umetsu, D.T. Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17. J. Exp. Med., 205, 385-393 (2008).
16) Aujla, S.J., Chan, Y.R., Zheng, M., Fei, M., Askew, D.J., Pociask, D.A., Reinhart, T.A., McAllister, F., Edeal, J., Gaus, K., Husain, S., Kreindler, J.L., Dubin, PJ., Pilewski, J.M., Myerburg, M.M., Mason, C.A., Iwakura, Y., and Kolls, J.K. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat. Med., 14, 275-281 (2008).
17) Izcue, A., Hue, S., Buonocore, S., Arancibia-Carcamo, C.V., Ahern, P.P., Iwakura, Y., Maloy, K.J., Powrie, F. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity, 28, 559-570 (2008).
18) 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. Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J. Exp. Med., 205, 799-810 (2008).
19) Tajima, M., Wakita, D., Noguchi, D., Chamoto, K., Yue, Z., Fugo, K., Ishigame, H., Iwakura, Y., Kitamura, H., and Nishimura, T. IL-6?dependent spontaneous proliferation is required for the induction of colitogenic IL-17?producing CD8+ T cells. J. Exp. Med., 205, 1019-1027 (2008).
20) Lees, J.R., Iwakura, Y., and Russell, J.H. 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. J. Immunol., 180, 8066-8072 (2008).
21) Doodes, P.D., Cao, Y., Hamel K.M., Wang Y., Farkas, B., Iwakura, Y., and Finnegan, A. Development of Proteoglycan-Induced Arthritis Is Independent of IL-17. J. Immunol., 181, 329-337 (2008).
22) Bai, Y., Liu, R., Huang, D., La Cava, A., Tang, Y.Y., Iwakura, Y., Campagnolo, D.I., Vollmer, T.L., Ransohoff, R.M., and Shi, F.D. CCL2 recruitment of IL-6-producing CD11b+ monocytes to the draining lymph nodes during the initiation of Th17-dependent B cell-mediated autoimmunity. Eur. J. Immunol., 38, 1877-1888 (2008).
23) Fukushima, A., Sumi, T., Ishida, W., Yamada, J., Iwakura, Y., and Ueno, H.? Endogenous IL-17 Does Not Play a Significant Role in the Development of Experimental Murine Allergic Conjunctivitis.? Int. Arch. Allergy Immunol., 147, 206-212 (2008).
24) Schulz, S.M., Kohler, G., Holscher, C., Iwakura, Y., and Alber, G. IL-17A is produced by Th17, γΒT cells and other CD4- lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearance. Int. Immunol., 20, 1129-1138 (2008).
25) Hamada, S., Umemura, M., Shiono, T., Tanaka, K., Yahagi, A., Begum, D.M., 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., and Matsuzaki, G. IL-17A Produced by γΒT Cells Plays a Critical Role in Innate Immunity against Listeria monocytogenes Infection in the Liver. J. Immunol., 181, 3456-3463 (2008).
26) Ogura, H., Murakami, M., Okuyama, Y., Tsuruoka, M., Kitabayashi, C., Kanamoto, M., Nishihara, M., Iwakura, Y., and Hirano, T. Interleukin-17 Promotes Autoimmunity by Triggering a Positive-Feedback Loop via Interleukin-6 Induction. Immunity, 29, 628-636 (2008).
27) Iwakura, Y., Nakae, S., Saijo, S., and Ishigame, H.?The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol. Rev., 226, 57-79 (2008).
28) Wakashin, H., Hirose, K., Maezawa, Y., Kagami, S.I., Suto, A., Watanabe, N., Saito, Y., Hatano, M., Tokuhisa, T., Iwakura, Y., Puccetti, P., Iwamoto, I., and Nakajima, H. IL-23 and Th17 Cells Enhance Th2 Cell-mediated Eosinophilic Airway Inflammation in Mice. Am. J. Respir. Crit. Care Med., 178, 1023-1032 (2008).
29) 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., and Mazda, O. Involvement of IL-17A in the pathogenesis of DSS-induced colitis in mice. Biochem. Biophys. Res. Commun., 377, 12-16 (2008).
30) 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., and Alber, G.? Protective Immunity to Systemic Infection with Attenuated Salmonella enterica serovar Enteritidis in the Absence of IL-12 Is Associated with IL-23-Dependent IL-22, but Not IL-17. J. Immunol., 181, 7891-7901 (2008).
31) Shiomi, S., Toriie, A., Imamura, S., Konishi, H., Mitsufuji, S., Iwkaura, Y., Yamaoka, Y., Ota, H., Yamamoto, T., Imanishi, J., and Kita, M. IL-17 is Involved in Helicobacter pylori-Induced Gastric Inflammatory Responses in a Mouse Model. Helicobacter, 13, 518-524 (2008).
32) Ishigame, H., Kakuta, S., Nagai, T., Kadoki, M., Nambu, A., Komiyama, Y., Fujikado, N., Tanahashi, Y., Akitsu, A., Kotaki, H., Sudo, K., Nakae, S., Sasakawa, C., and Iwakura, Y. Differential Roles of Interleukin-17A and -17F in Host Defense against Mucoepithelial Bacterial Infection and Allergic Responses. Immunity, 30, 108-119 (2009).
33) Kappel, L.W., Goldberg, G.L., King, C.G., Suh, D.Y., Smith, O.M., Ligh, C., Holland, A.M., Grubin, J., Mark, N.M., Liu, C., Iwakura, Y., Heller, G., and van den Brink, M.R. IL-17 contributes to CD4-mediated graft-versus-host disease. Blood, 113, 945-952 (2009).
34) Lopez Kostka, S., Dinges, S., Griewank, K., Iwakura, Y., Udey, M.C., and von Stebut, E. IL-17 Promotes Progression of Cutaneous Leishmaniasis in Susceptible Mice. J. Immunol., 182, 3039-3046 (2009).
35) Yamada, J., Hamuro, J., Fukushima, A., Ohteki, T., Terai, K., Iwakura, Y., Yagita, H., and Kinoshita, S. MHC-matched corneal allograft rejection in an IFN-γ/IL-17-independent manner in C57BL/6 mice. Invest. Ophthalmol. Vis. Sci., 50, 2139-2146 (2009).
36) O'Connor, W. Jr, Kamanaka, M., Booth, C.J., Town, T., Nakae, S., Iwakura, Y., Kolls, J.K., and Flavell, R.A. A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat. Immunol., 10, 603-609 (2009).
37) Oseko, F., Yamamoto, T., Akamatsu, Y., Kanamura, N., Iwakura, Y., Imanishi, J., and Kita, M. IL-17 is involved in bone resorption in mouse periapical lesions. Microbiol. Immunol., 53, 287-294 (2009).
38) Okiyama, N., Sugihara, T., Iwakura, Y., Yokozeki, H., Miyasaka, N., and Kohsaka, H. Therapeutic effects of interleukin-6 blockade in a murine model of polymyositis that does not require interleukin-17A. Arthritis Rheum., 60, 2505-2512 (2009).
39) Shichita, T., Sugiyama, Y., Ooboshi, H., Sugimori, H., Nakagawa, R., Takada, I., Iwaki, T., Okada, Y., Iida, M., Cua, D.J., Iwakura, Y., and Yoshimura, A. Pivotal role of cerebral interleukin-17-producing γΒT cells in the delayed phase of ischemic brain injury. Nat. Med., 15, 946-950 (2009).
40) Yi, T., Chen, Y., Wang, L., Du, G., Huang, D., Zhao, D., Johnston, H., Young, J., Todorov, I., Umetsu, D.T., Chen, L., Iwakura, Y., Kandeel, F., Forman, S., and Zeng, D. Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft versus host disease. Blood, 114, 3101-3112 (2009).
41) Horie, I., Abiru, N., Nagayama, Y., Kuriya, G., Saitoh, O., Ichikawa, T., Iwakura, Y., and Eguchi, K. T Helper Type 17 Immune Response Plays an Indispensable Role for Development of Iodine-Induced Autoimmune Thyroiditis in Nonobese Diabetic-H2h4 Mice. Endocrinology, 150, 5135-5142 (2009).
42) 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., and Khader, S.A. Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensis. Immunity, 31, 799-810 (2009).
43) Tanaka, S., Yoshimoto, T., Naka, T., Nakae, S., Iwakura, Y., Cua, D., and Kubo, M. Natural occurring IL-17 producing T cells regulate the initial phase of neutrophil mediated airway responses. J. Immunol., 183, 7523-7530 (2009).
44) Faust, S.M., Lu, G., Marini, B.L., Zou, W., Gordon, D., Iwakura, Y., Laouar, Y., and Bishop, D.K. Role of T cell TGFΐ signaling and IL-17 in allograft acceptance and fibrosis associated with chronic rejection. J. Immunol., 183, 7297-7306 (2009).
45) Oyamada, A., Ikebe, H., Itsumi, M., Saiwai, H., Okada, S., Shimoda, K., Iwakura, Y., Nakayama, K.I., Iwamoto, Y., Yoshikai, Y., and Yamada, H. Tyrosine kinase 2 plays critical roles in the pathogenic CD4 T cell responses for the development of experimental autoimmune encephalomyelitis. J. Immunol., 183, 7539-7546 (2009).
46) 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., and Liesenfeld, O. Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. J. Exp. Med., 206, 3047-3059 (2009).
47) Doodes, P.D., Cao, Y., Hamel, K.M,, Wang, Y., Rodeghero, R.L., Mikecz, K., Glant, T.T., Iwakura, Y., and Finnegan, A. IFN-γ Regulates the Requirement for IL-17 in Proteoglycan-Induced Arthritis. J. Immunol., 184, 1552-1559 (2010).
48) Madhur, M.S., Lob, H.E., McCann, L.A., Iwakura, Y., Blinder, Y., Guzik, T.J., and Harrison, D.G. Interleukin 17 Promotes Angiotensin II-Induced Hypertension and Vascular Dysfunction. Hypertension, 55, 500-507 (2010).
49) 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., and Fischbein, M.P. IL-17 Contributes to the Development of Chronic Rejection in a Murine Heart Transplant Model. J. Clin. Immunol., 22, 157-166 (2010).
50) Adamopoulos, I.E., Chao, C.C., Geissler, R., Laface, D., Blumenschein, W., Iwakura, Y., McClanahan, T., and Bowman, E.P. Interleukin-17A upregulates receptor activator of NF-ΘB on osteoclast precursors. Arthritis Res. Ther., 12, R29 (2010).
51) Teng, M.W., Andrews, D.M., McLaughlin, N., von Scheidt, B., Ngiow, S.F., Moller, A., Hill, G.R., Iwakura, Y., Oft, M., and Smyth, M.J. IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasis. Proc. Natl. Acad. Sci. USA, 107, 8328-8333 (2010).
52) Baldeviano, G.C., Barin, J.G., Talor, M.V., Srinivasan, S., Bedja, D., Zheng, D., Gabrielson, K., Iwakura, Y., Rose, N.R., and Cihakova, D. Interleukin-17A Is Dispensable for Myocarditis but Essential for the Progression to Dilated Cardiomyopathy. Circ. Res., 106, 1646-1655 (2010).
53) Cowley, S.C., Meierovics, A.I., Frelinger, J.A., Iwakura, Y., and Elkins, K.L. Lung CD4-CD8- Double-Negative T Cells Are Prominent Producers of IL-17A and IFN-γ during Primary Respiratory Murine Infection with Francisella tularensis Live Vaccine Strain. J. Immunol., 184, 5791-5801 (2010).
54) Ashino, S., Wakita, D., Shiohama, Y., Iwakura, Y., Chamoto, K., Ohkuri, T., Kitamura, H., and Nishimura, T. A Th17-polarized cell population that has infiltrated the lung requires cells that convert to IFN-γ production in order to induce airway hyperresponsiveness. Int. Immunol., 22, 503-513 (2010).
55) Gan, P.Y., Steinmetz, O.M., Tan, D.S., O'Sullivan, K.M., Ooi, J.D., Iwakura, Y., Kitching, A.R., and Holdsworth, S.R. Th17 Cells Promote Autoimmune Anti-Myeloperoxidase Glomerulonephritis. J. Am. Soc. Nephrol., 21, 925-931 (2010).
56) Wakita, D., Sumida, K., Iwakura, Y., Nishikawa, H., Ohkuri, T., Chamoto, K., Kitamura, H., and Nishimura T. Tumor-infiltrating IL-17-producing γΒ T cells support the progression of tumor via promoting angiogenesis. Eur. J. Immunol.,40, 1927-1937 (2010).
57) Hill, G.R., Olver, S.D., Kuns, R.D., Varelias, A., Raffelt, N.C., Don, A.L., Markey, K.A., Wilson, Y.A., Smyth, M.J., Iwakura, Y., Tocker, J., Clouston, A.D., and Macdonald, K.P. Stem cell mobilization with G-CSF induces Type-17 differentiation and promotes scleroderma. Blood, 116, 819-828 (2010).
58) Miyazaki, Y., Hamano, S., Wang, S., Shimanoe, Y., Iwakura, Y., and Yoshida, H. IL-17 Is Necessary for Host Protection against Acute-Phase Trypanosoma cruzi Infection. J. Immunol., 185, 1150-1157 (2010).
59) Oh, I., Ozaki, K., Meguro, A., Hatanaka, K., Kadowaki, M., Matsu, H., Tatara, R., Sato, K., Iwakura, Y., Nakae, S., Sudo, K., Teshima, T., Leonard, W.J., and Ozawa, K. Altered Effector CD4+ T Cell Function in IL-21R-/- CD4+ T Cell-Mediated Graft-Versus-Host Disease. J. Immunol., 185, 1920-1926.
61) Dunne, A., Ross, P.J., Pospisilova, E., Masin, J., Meaney, A., Sutton, C.E., Iwakura, Y., Tschopp, J., Sebo, P., and Mills, K.H. Inflammasome Activation by Adenylate Cyclase Toxin Directs Th17 Responses and Protection against Bordetella pertussis. J. Immunol., 185, 1711-1719 (2010).
62) Henningsson, L., Jirholt, P., Lindholm, C., Eneljung, T., Silverpil, E., Iwakura, Y., Linden, A., and Gjertsson, I. Interleukin-17A during local and systemic Staphylococcus aureus-induced arthritis in mice. Infect. Immun., 78, 3783-3790 (2010).
63) Vokaer, B., Van Rompaey, N., Lemaitre, P.H., Lhomme, F., Kubjak, C., Benghiat, F.S., Iwakura, Y., Petein, M., Field, K.A., Goldman, M., Le Moine, A., and Charbonnier, L.M. Critical Role of Regulatory T Cells in Th17-Mediated Minor Antigen-Disparate Rejection. J. Immunol., 185, 3417-3425 (2010).
64) Narita, K., Hu, D.L., Mori, F., Wakabayashi, K., Iwakura, Y., and Nakane, A. Role of IL-17A in Cell-Mediated Protection against Staphylococcus aureus Infection in Mice Immunized with Fibrinogen Binding Domain of Clumping Factor A. Infect. Immun., 78, 4234-4242 (2010).
65) Echeverry, A., Saijo, S., Schesser, K., and Adkins, B. Yersinia enterocolitica promotes robust mucosal inflammatory T-cell immunity in murine neonates. Infect. Immun., 78, 3595-3608 (2010).
66) Lee, H.H., Meyer, E.H., Goya, S., Pichavant, M., Kim, H.Y., Bu, X., Umetsu, S.E., Jones, J.C., Savage, P.B., Iwakura, Y., Casasnovas, J.M., Kaplan, G., Freeman, G.J., Dekruyff, R.H., and Umetsu, D.T. Apoptotic Cells Activate NKT Cells through T Cell Ig-Like Mucin-Like-1 Resulting in Airway Hyperreactivity. J. Immunol., 185, 5225-5235 (2010).
67) Ikeda, U., Wakita, D., Ohkuri, T., Chamoto, K., Kitamura, H., Iwakura, Y., and Nishimura, T. 1α,25-Dihydroxyvitamin D3 and all-trans retinoic acid synergistically inhibit the differentiation and expansion of Th17 cells. Immunol. Lett., 134, 7-16 (2010).
68) Ishida, H., Matsuzaki-Moriya, C., Imai, T., Yanagisawa, K., Nojima, Y., Suzue, K., Hirai, M., Iwakura, Y., Yoshimura, A., Hamano, S., Shimokawa, C., and Hisaeda, H. Development of experimental cerebral malaria is independent of IL-23 and IL-17. Biochem. Biophys. Res. Commun., 402, 790-795 (2010).
69) Sun, X., Yamada, H., Shibata, K., Muta, H., Tani, K., Podack, E.R., Iwakura, Y., and Yoshikai, Y. CD30 Ligand Is a Target for a Novel Biological Therapy against Colitis Associated with Th17 Responses. J. Immunol., 185, 7671-7680 (2010).
70) Horie, I., Abiru, N., Saitoh, O., Ichikawa, T., Iwakura, Y., Eguchi, K., and Nagayama, Y. Distinct role of T helper Type 17 immune response for Graves' hyperthyroidism in mice with different genetic backgrounds. Autoimmunity, 44, 159-165 (2011).
71) Murakami, M., Okuyama, Y., Ogura, H., Asano, S., Arima, Y., Tsuruoka, M., Harada, M., Kanamoto, M., Sawa, Y., Iwakura, Y., Takatsu, K., Kamimura, D., and Hirano, T. Local microbleeding facilitates IL-6- and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells. J. Exp. Med., 208, 103-114 (2011).
73) Zhou, Y., Sonobe, Y., Akahori, T., Jin, S., Kawanokuchi, J., Noda, M., Iwakura, Y., Mizuno, T., and Suzumura, A. IL-9 Promotes Th17 Cell Migration into the Central Nervous System via CC Chemokine Ligand-20 Produced by Astrocytes. J. Immunol., 186, 4415-4421 (2011).
74) Fei, M., Bhatia, S., Oriss, T.B., Yarlagadda, M., Khare, A., Akira, S., Saijo, S., Iwakura, Y., Fallert Junecko, B.A., Reinhart, T.A., Foreman, O., Ray, P., Kolls, J., and Ray, A. TNF-α from inflammatory dendritic cells (DCs) regulates lung IL-17A/IL-5 levels and neutrophilia versus eosinophilia during persistent fungal infection. Proc. Natl. Acad. Sci. USA., 108, 5360-5365 (2011).
jLECT2Ή}EX
1) Saito, T., Okumura, A., Watanabe, H., Asano, M., Ishida-Okawara, A., Sakagami, J., Sudo, K., Hatano-Yokoe, Y., Bezbradica, J.S., Joyce, S., Abo, T., Iwakura, Y., Suzuki, K., and Yamagoe, S. Increase in Hepatic NKT Cells in Leukocyte Cell-Derived Chemotaxin 2-Deficient Mice Contributes to Severe Concanavalin A-Induced Hepatitis. J. Immunol., 173, 579-585 (2004).
2) Okumura, A., Saito, T., Otani, I., Kojima, K., Yamada, Y., Ishida-Okawara, A., Nakazato, K., Asano, M., Kanayama, K., Iwakura, Y., Suzuki, K., and Yamagoe, S.? Suppressive role of leukocyte cell-derived chemotaxin 2 in mouse anti-type II collagen antibody-induced arthritis.? Arthritis Rheum.,?58, 413-421 (2008).
j2-5OASΉ}EX
@@ Oas1aAOas1cAOas2AOas1a/Oas2
ζ25ρϊ{ͺqΆ¨wοi2002Nj@v|W p.961
ζ26ρϊ{ͺqΆ¨wοi2003Nj@v|W p.788
jCXCR4/flox}EX
1) Bai, Z., Hayasaka, H., Kobayashi, M., Li, W., Guo, Z., Jang, M.H., Kondo, A., Choi, B.I., Iwakura, Y., and Miyasaka, M. CXC Chemokine Ligand 12 Promotes CCR7-Dependent Naive T Cell Trafficking to Lymph Nodes and Peyer's Patches. J. Immunol., 182, 1287-1295 (2009).
jDok2Ή}EX
1) Yasuda, T., Shirakata, M., Iwama, A., Ishii, A., Ebihara, Y., Osawa, M., Honda, K., Shinohara, H., Sudo, K., Tsuji, K., Nakauchi, H., Iwakura, Y., Hirai, H., Oda, H., Yamamoto, T., and Yamanashi, Y. Role of Dok-1 and Dok-2 in Myeloid Homeostasis and Suppression of Leukemia. J. Exp. Med., 200, 1681-1687 (2004).
2) Shinohara, H., Inoue, A., Toyama-Sorimachi, N., Nagai, Y., Yasuda, T., Suzuki, H., Horai, R., Iwakura, Y., Yamamoto, T., Karasuyama, H., Miyake, K., and Yamanashi, Y. Dok-1 and Dok-2 are negative regulators of lipopolysaccharide-induced signaling. J. Exp. Med., 201, 333-339 (2005).
jDectin-1Ή}EX
1) Saijo, S., Fujikado, N., Furuta, T., Chung, S., Kotaki, H., Seki, K., Sudo, K., Akira, S., Adachi, Y., Ohno, N., Kinjo, T., Nakamura, K., Kawakami, K., and Iwakura, Y. Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat. Immunol., 8, 39-46 (2007).
2) Hara, H., Ishihara, C., Takeuchi, A., Imanishi, T., Xue, L., Morris, SW., Inui, M., Takai, T., Shibuya, A., Saijo, S., Iwakura, Y., Ohno, N., Koseki, H., Yoshida, H., Penninger JM., and Saito, T.? The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors. Nat. Immunol., 8, 619-629 (2007).
3) Nakamura, K., Kinjo, T., Saijo, S., Miyazato, A., Adachi, Y., Ohno, N., Fujita, J., Kaku, M,. Iwakura, Y., and Kawakami, K. Dectin-1 Is Not Required for the Host Defense to Cryptococcus neoformans. Microbiol. Immunol., 51, 1115-1119 (2007).
4) Nakamura, K., Miyazato, A., Gang, X., Hatta, M., Iden, K., Aoyagi, T., Shiratori, K., Takeda, K., Akira, S., Saijo, S., Iwakura, Y., Adachi, Y., Ohno, N., Suzuki, K., Fujita, J., Kaku, M., and Kawakami, K. Deoxynucleic Acids from Cryptococcus neoformans Activate Myeloid Dendritic Cells via a TLR9-Dependent Pathway. J. Immunol., 180, 6067-4074 (2008).
5) Nakamura, K., Miyazato, A., Koguchi, Y., Adachi, Y., Ohno, N., Saijo, S., Iwakura, Y., Takeda, K., Akira, S., Fujita, J., Ishii, K., Kaku, M., and Kawakami, K. 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. Microbes Infect., 10, 1223-1227 (2008).
6) Miyazato, A., Nakamura, K., Yamamoto, N., Mora-Montes, H.M., 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, N.A., Kaku, M., and Kawakami, K. Toll-like receptor 9-dependent activation of myeloid dendritic cells by deoxynucleic acids from Candida albicans. Infect. Immun., 77, 3056-3064 (2009).
7) Xiao, G., Miyazato, A., Abe, Y., Zhang, T., Nakamura, K., Inden, K., Tanaka, M., Tanno, D., Miyasaka, T., Ishii, K., Takeda, K., Akira, S., Saijo, S., Iwakura, Y., Adachi, Y., Ohno, N., Yamamoto, N., Kunishima, H., Hirakata, Y., Kaku, M., and Kawakami, K. Activation of myeloid dendritic cells by deoxynucleic acids from Cordyceps sinensis via a Toll-like receptor 9-dependent pathway. Cell. Immunol., 263, 241-250 (2010).
8) Rivera, A., Hohl, T.M., Collins, N., Leiner, I., Gallegos, A., Saijo, S., Coward, J.W., Iwakura, Y., and Pamer, E.G. Dectin-1 diversifies Aspergillus fumigatus-specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation. J. Exp. Med., 208, 369-381 (2011).
9) Bhatia, S., Fei, M., Yarlagadda, M., Qi, Z., Akira, S., Saijo, S., Iwakura, Y., van Rooijen, N., Gibson, G.A., St Croix, C.M., Ray, A., and Ray, P. Rapid host defense against Aspergillus fumigatus involves alveolar macrophages with a predominance of alternatively activated phenotype. PLoS One, 6, e15943 (2011).
10) Drummond, R.A., Saijo, S., Iwakura, Y., and Brown, G.D. The role of Syk/CARD9 coupled C-type lectins in antifungal immunity. Eur. J. Immunol., 41, 276-281 (2011).
jLGP2Ή}EX
1) Venkataraman, T., Valdes, M., Elsby, R., Kakuta, S., Caceres, G., Saijo, S., Iwakura, Y., and Barber, GN. Loss of DExD/H Box RNA Helicase LGP2 Manifests Disparate Antiviral Responses. J. Immunol., 178, 6444-55 (2007).
jCCR8Ή}EX
ζ36ρϊ{Ζuwοi2006Nj@v|W p.300
pjDectin-2Ή}EX
1) 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., and Yoichiro Iwakura. Dectin-2 Recognition of α-Mannans and Induction of Th17 Cell Differentiation Is Essential for Host Defense against Candida albicans. Immunity, 32, 681-691 (2010).