121. Sugawara, I., Yamada, H., Mizuno, S., Takeda, K., and Akira, S.: Mycobacterial infection in MyD88-deficient mice. Microbiol. Immunol. 47, 841-847 (2003).
120. Iiyama, R., Kanai, T., Uraushihara, K., Ishikura, T., Makita, S., Totsuka, T., Yamazaki, M., Nakamura, T., Miyata, T., Yoshida, H., Takeuchi, O., Hoshino, K., Takeda, K., Ishikawa, H., Akira, S., and Watanabe, M.: Normal development of the gut-associated lymphoid tissue except Peyer's patch in MyD88-deficient mice. Scand. J. Immunol. 58, 620-627 (2003).
119. Suzuki, N., Suzuki, S., Eriksson, U., Hara, H., Mirtosis, C., Chen, N.-J., Wada, T., Bouchard, D., Hwang, I., Takeda, K., Fujita, T., Der, S., Penninger, J. M., Akira, S., Saito, T., and Yeh, W-C.: IL-1R-associated kinase 4 is required for lipopolysaccharide-induced activation of APC. J. Immunol. 171, 6065-6071 (2003).
118. Joosten, L. A. B., Koenders, M. I., Smeets, R. L., Heuvelmans-Jacobs, M., Helsen, M. M. A., Takeda, K., Akira, S., Lubberts, E., van de Loo, F. A. J., and van den Berg, W. B.: Toll-like receptor 2 pathway drives Streptococal cell wall-induced joint inflammation: Critical role of MyD88. J. Immunol. 171, 6145-6153 (2003).
117. Matsukawa, A., Takeda, K., Kudo, S., Maeda, T., Kagayama, M., and Akira, S.: Aberrant inflammation and lethality to septic peritonitis in mice lacking Stat3 in macrophages and neutrophils. J. Immunol. 171, 6198-6205 (2003).
116. Kuwata, H., Watanabe, Y., Miyoshi, H., Yamamoto, M., Kaisho, T., Takeda, K., and Akira, S.: IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-a production in macrophages. Blood 102, 4123-4129 (2003).
115. Yamamoto, M., Sato, S., Hemmi, H., Uematsu, S., Hoshino, K., Kaisho, T., Takeuchi, O., Takeda, K., and Akira, S.: TRAM is specifically involved in the TLR4-mediated MyD88-independent signaling pathway. Nat. Immunol. 4, 1144-1150 (2003).
114. Heil, F., Ahmad-Nejad, P., Hemmi, H., Hochrein, H., Ampenberger, F., Gellert, T., Dietrich, H., Lipford, G., Takeda, K., Akira, S., Wagner, H., and Bauer, S.: The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily. Eur. J. Immunol. 33, 2987-2997 (2003).
113. Shi, S., Nathan, C., Schnappinger, D., Drenkow, J., Fuortes, M., Block, E., Ding, A., Gingeras, T. R., Schoolnik, G., Akira, S., Takeda, K., and Ehrt, S.: MyD88 primes macrophages for full-scale activation by interferon-g yet mediates few responses to Mycobacterium tuberculosis. J. Exp. Med. 198, 987-997 (2003).
112. Sato, S., Sugiyama, M., Yamamoto, M., Watanabe, Y., Kawai, T., Takeda, K., and Akira, S.: Toll/IL-1 receptor domain-containing adaptor inducing IFN-b (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kB and IFN-regulatory factor-3, in the Toll-like receptor signaling. J. Immunol. 171, 4304-4310 (2003).
111. Haga, S., Terui, K., Zhang, H. Q., Enosawa, S., Ogawa, W., Inoue, H., Okuyama, T., Takeda, K., Akira, S., Ogino, T., Irani, K., and Ozaki, M.: Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms. J. Clin. Invest. 112, 989-998 (2003).
110. 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-g. Int. Immunol. 15, 1183-1194 (2003).
109. Weijer, S., Sewnath, M. E., de Vos, A. F., Florquin, S., van der Sluis, K., Gouma, D. J., Takeda, K., Akira, S., and van der Poll, T.: Interleukin-18 facilitates the early antimicrobial host response to Escherichia coli peritonitis. Infect. Immun. 71, 5488-5497 (2003).
108. Chen, F., Wang H.-W., Cuenca, A., Wang, H., Huang, M., Ghansah, T., Brayer, J., Kerr, W. G., Takeda, K., Akira, S., Schoenberger, S., Yu, H., Jove, R., and Sotomayor, E. M.: A critical role for STAT3 signaling in immune tolerance. Immunity 19, 425-436 (2003).
107. Shibue, T., Takeda, K., Oda, E., Tanaka, H., Murasawa, H., Takaoka, A., Morishita, Y., Akira, S., Taniguchi, T., and Tanaka, N.: Integral role of Noxa in p53-mediated apoptotic response. Genes Dev. 17, 2233-2238 (2003).
106. Takagi, H., Kanai, T., Okazawa, A., Kishi, Y., Sato, T., Takaishi, H., Inoue, N., Ogata, H., Iwao, Y., Hoshino, K., Takeda, K., Akira, S., Watanabe, M., Ishii, H., and Hibi, T.: Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulphate colitis in mice. Scand. J. Gastroenterol. 38, 837-844 (2003).
105. Yamamoto, M., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Sanjo, H., Takeuchi, O., Sugiyama, M., Okabe, M., Takeda, K., and Akira, S.: Role of adaptor TRIF in the MyD88-independent Toll-like receptor signaling pathway. Science 301, 640-643 (2003).
104. Zhang, J. H., He, H., Borzychowski, A. M., Takeda, K., Akira, S., and Croy, B. A.: Analysis of cytokine regulators inducing interferon production by mouse uterine natural killer cells. Biol. Reprod. 69, 404-411 (2003).
103. Kojima, E., Takeuchi, A., Haneda, M., Yagi, F., Hasegawa, T., Yamaki, K., Takeda, K., Akira, S., Shimokata, K., and Isobe, K.: The function of GADD34 is a recovery from a shut-off of protein synthesis induced by ER stress; elucidation by GADD34-deficient mice. FASEB J. 17, 1573-1575 (2003).
102. Yazawa, N., Fujimoto, M., Sato, S., Miyake, K., Asano, N., Takeuchi, O., Takeda, K., Akira, S., Tedder, T. F., Tamaki, K.: CD19 regulates innate immunity by the Toll-like receptor RP105 signaling in B lymphocytes. Blood 102, 1374-1380 (2003).
101. Elhage, R., Jawien, J., Rudling, M., Ljunggren, H. G., Takeda, K., Akira, S., Bayard, F., and Hansson, G. K.: Reduced atherosclerosis in interleukin-18 deficient apolipoprotein E-knockout mice. Cardiovasc. Res. 59, 234-240 (2003).
100. Yokozeki, H., Wu, M. H., Sumi, K., Igawa, K., Miyazaki, Y., Katayama, I., Takeda, K., Akira, S., and Nishioka, K.: Th2 cytokines, IgE and mast cells play a crucial role in the induction of para-phenylenediamine-induced contact hypersensitivity in mice. Clin. Exp. Immunol. 132, 385-392 (2003).
99. Yasukawa, H., Ohishi, M., Mori, H., Murakami, M., Chinen, T., Aki, D., Hanada, T., Takeda, K., Akira, S., Hoshijima, M., Hirano, T., Chien, K. R., Yoshimura, A.: IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nat. Immunol. 4, 551-556 (2003).
98. Zwijnenburg, P. J. G., van der Poll, T., Florquin, S., Akira, S., Takeda, K., Roord, J. J., and van Furth, A. M.: Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis. J. Neuroimmunol. 138, 31-37 (2003).
97. Wheeler, R. D., Brough, D., Le Feuvre, R. A., Takeda, K., Iwakura, Y., Luheshi, G. N., and Rothwell, N. J.: Interleukin-18 induces expression and release of cytokines from murine glial cells: interactions with interleukin-1b. J. Neurochem. 85, 1412-1420 (2003).
96. Kobayashi, M., Kweon, M., Kuwata, H., Kiyono, H., Takeda, K., and Akira, S.: Toll-like receptor-dependent IL-12p40 production causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice. J. Clin. Invest. 111, 1297-1308 (2003).
95. Wheeler, R. D., Boutin, H., Touzani, O., Luheshi, G. N., Takeda, K., and Rothwell, N. J.: No role for interleukin-18 in acute murine stroke-induced brain injury. J. Cereb. Blood Flow Metab. 23, 531-535 (2003).
94. Schultz, M., J., Knapp, S., Florquin, S., Pater, J., Takeda, K., Akira, S., and van der Poll, T.: Interleukin-18 impairs the pulmonary host response to Pseudomonas aeruginosa. Infect. Immun. 71, 1630-1634 (2003).
93. Hemmi, H., Kaisho, T., Takeda, K., and Akira, S.: The roles of Toll-like receptor 9, MyD88, and DNA-PKcs in the effects of two distinct CpG DNAs on dendritic cell subsets. J. Immunol. 170, 3059-3064 (2003).
92. Hazeki, K., Masuda, N., Funami, K., Sukenobu, N., Matsumoto, M., Akira, S., Takeda, K., Seya, T., and Hazeki, O.: Toll-like receptor-mediated tyrosine phosphorylation of paxillin via MyD88-dependent and -independent pathways. Eur. J. Immunol. 33, 740-747 (2003).
91. Prinz, M., Heikenwaelder, M., Schwarz, P., Takeda, K., Akira, S., and Aguzzi, A.: Prion pathogenesis in the absence of Toll-like receptor signaling. EMBO Rep. 4, 195-199 (2003).
90. Sanjo, H., Takeda, K., Tsujimura, T., Ninomiya-Tsuji, J., Matsumoto, K., and Akira, S: TAB2 is essential for prevention of apoptosis in fetal liver but not for IL-1 signaling. Mol. Cell. Biol. 23, 1231-1238 (2003).
89. Okuda, Y., Takahashi, I., Kim, J. -K., Ohta, N., Iwatani, K., Iijima, H., Kai, Y., Tamagawa, H., Hiroi, T., Kweon, M. -N., Kawano, S., Takeda, K., Akira, S., Sasaki, Y., Hori, S., and Kiyono, H.: Development of colitis in STAT6-deficient TCRa-/- mice: a potential role of STAT6-independent IL-4 signaling for the generation of Th2-biased pathologic CD4+bb T cells. Am. J. Pathol. 162, 263-271 (2003).
88. Yamamoto, M., Sato, S., Mori, K., Takeuchi, O., Hoshino, K., Takeda, K., and Akira, S.: A novel Toll/IL-1 receptor domain-containing adaptor that preferentially activates the IFN-b promoter in the Toll-like receptor signaling. J. Immunol. 169, 6668-6672 (2002).
87. Yamamoto, M., Sato, S., Hemmi, H., Sanjo, H., Uematsu, S., Kaisho, T., Hoshino, K., Takeuchi, O., Kobayashi, M., Fujita, T., Takeda, K., and Akira, S.: Essential role for TIRAP in activation of the signaling cascade shared by TLR2 and TLR4. Nature 420, 324-329 (2002).
86. Yamao, T., Noguchi, T., Takeuchi, O., Nishiyama, U., Morita, H., Hagiwara, T., Akahori, H., Kato, T., Inagaki, K., Okazawa, H., Hayashi, Y., Matozaki, T., Takeda, K., Akira, S., and Kasuga, M.: Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1. J. Biol. Chem. 277, 39833-39839 (2002).
85. Nakagawa, R., Naka, T., Tsutsui, H., Fujimoto, M., Kimura, A., Abe, T., Seki, E., Sato, S., Takeuchi, O., Takeda, K., Akira, S., Yamanishi, K., Kawase, I., Nakanishi, K., Kishimoto, T.: SOCS-1 participates in negative regulation of LPS responses. Immunity 17, 677-687 (2002).
84. Konishi, H., Tsutsui, H., Murakami, T., Yumikura-Futatsugi, S., Yamanaka, K. I., Tanaka, M., Iwakura, Y., Suzuki, N., 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. U S A. 99, 11340-11345 (2002).
83. Wang, T., Lafuse, W. P., Takeda, K., Akira, S., and Zwilling, B. S.: Rapid chromatin remodeling of Toll-like receptor 2 promoter during infection of macrophages with Mycobacterium avium. J. Immunol. 169, 795-801 (2002).
82. Suzuki, K., Nakajima, H., Kagami, S., Suto, A., Ikeda, K., Hirose, K., Hiwasa, T., Takeda, K., Saito, Y., Akira, S. and Iwamoto, I.: Proteolytic processing of Stat6 signaling in mast cells as a negative regulatory mechanism. J. Exp. Med. 196, 27-38 (2002).
81. Sato, S., Takeuchi, O., Fujita, T., Tomizawa, H., Takeda, K., Akira, S. A variety of microbial components induce tolerance to lipopolysaccharide by differentially affecting MyD88-dependent and ?independent pathways. Int. Immunol. 14, 783-791 (2002).
80. Kinjo, Y., Kawakami, K., Uezu, K., Yara, S., Miyagi, K., Kogichi, Y., Hoshino, T., Okamoto, M., Kawase, Y., Yokota, K., Yoshino, K., Takeda, K., Akira, S., and Saito, A.: Contribution of IL-18 to Th1 response and host defense against infection by Mycobacterium tuberculosis: a comparative study with IL-12 p40. J. Immunol. 169, 323-329 (2002).
79. Takeuchi, O., Sato, S., Horiuchi, T., Hoshino, K., Takeda, K., Dong, Z., Modlin, R. L., and Akira, S.: Role of TLR1 in mediating immune response to microbial lipoproteins. J. Immunol. 169, 10-14 (2002).
78. Uematsu, S., Matsumoto, M., Takeda, K., and Akira, S.: LPS-dependent prostaglandin E2 production is regulated by the glutathione-dependent prostaglandin E2 synthase gene induced by the TLR4/MyD88/NF-IL6 pathway. J. Immunol. 168, 5811-5816 (2002).
77. Yamazaki, T., Takeda, K., Gotoh, K., Takeshima, H., Akira, S., and Kurosaki, T.: Essential immunoregulatory role for BCAP in B cell development and function. J. Exp. Med. 195, 535-545 (2002).
76. Oyadomari, S., Koizumi, A., Takeda, K., Gotoh, T., Akira, S., Araki, E., and Mori, M.: Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes. J. Clin. Invest. 109, 525-532 (2002).
75. Hemmi, H., Kaisho, T., Takeuchi, O., Sato, S., Sanjo, H., Hoshino, K., Horiuchi, T., Tomizawa, H., Takeda, K., and Akira, S.: Small anti-viral compounds activate immune cells via the TLR7-MyD88-dependent signaling pathway. Nature Immunol. 3, 196-200 (2002).
74. Le Feuvre, R. A., Brough, D., Iwakura, Y., Takeda, K., and Rothwell, N. J.: Priming of macrophages with LPS potentiates P2X7 mediated cell death via a caspase-1 dependent mechanism, independently of cytokine production. J. Biol. Chem. 277, 3210-3218 (2002).
73. Schweizer, U., Gunnersen, J., Karch, C., Wiese, S., Holtmann, B., Takeda, K., Akira, S., and Sendtner, M.: Conditional gene ablation of Stat3 reveals differential signaling requirements for survival of motoneurons during development and after nerve injury in the adult. J. Cell Biol. 156, 287-298 (2002).
72. Toda, K., Takeda, K., Akira, S., Saibara, T., Okada, T., Onishi, S., and Shizuta, Y.: Alternations in hepatic expression of fatty-acid metabolizing enzymes in ArKO mice and their reversal by the treatment with 17b-estradiol or a peroxisome proliferator. J. Steroid Biochem. Mol. Biol. 79, 11-17 (2001).
71. Nomi, M., Oishi, I., Kani, S., Suzuki, H., Matsuda, T., Yoda, A., Kitamura, M., Itoh, K., Takeuchi, S., Takeda, K., Akira, S., Ikeya, M., Takada, S., and Minami, Y. : Loss of mRor1 enhances the heart and skeletal abnormalities in mRor2 deficient mice: Redundant and pleiotropic functions of mRor1 and mRor2 receptor tyrosine kinases. Mol. Cell. Biol. 21, 8329-8335 (2001).
70. Kanai, T., Watanabe, M., Okazawa, A., Sato, T., Yamazaki, M., Okamoto, S., Ishii, H., Totsuka, T., Iiyama, R., Okamoto, R., Ikeda, M., Kurimoto, M., Takeda, K., Akira, S., and Hibi, T.: Macrophage-derived IL-18 mediated intestinal inflammation in the murine model of Crohn's disease. Gastroenterology 121, 875-888 (2001).
69. Kawakami, K., Kinjo, Y., Yara, S., Uezu, K., Koguchi, Y., Tohyama, M., Azuma, M., Takeda, K., Akira, S., and Saito, A.: Enhanced IFN-g production through activation of Va14+ NK T cells by a-galactosylceramide in interleukin-18-deficient mice with systemic cryptococcosis. Infect. Immun. 69, 6643-6650 (2001).
68. Schnare, M., Barton, G. M., Holt, A. C., Takeda, K., Akira, S., and Medzhitov, R.: Toll-like receptors control activation of adaptive immune responses. Nature Immunol. 2, 947-950 (2001).
67. Mori, I., Hossain, J., Takeda, K., Okamura, H., Imai, Y., Kohsaka, S., and Kimura, Y.: Impaired microglial activation in the brain of IL-18-gene-disrupted mice after neurovirulent influenza A virus infection. Virology 287, 163-170 (2001).
66. Oyadomari, S., Takeda, K., Takiguchi, M., Gotoh, T., Matsumoto, M., Wada, I., Akira, S., Araki, E., Mori, M.: Nitric oxide-induced apoptosis in pancreatic beta cells is mediated by the endoplasmic reticulum stress pathway. Proc. Natl. Acad. Sci. USA 98, 10845-10850 (2001).
65. Byrd-Leifer, C. A., Block, E. F., Takeda, K., Akira, S., and Ding, A.: The role of MyD88 and TLR4 in the LPS-mimetic activity of taxol. Eur. J. Immunol. 31, 2448-2457 (2001).
64. Helmby, H., Takeda, K., Akira, S., and Grencis, R: Interleukin-18 promotes the development of chronic gastro-intestinal helminth infection by down-regulating IL-13. J. Exp. Med. 194, 355-364 (2001).
63. Toda, K., Takeda, K., Okada, T., Akira, S., Saibara, T., Kaname, T., Yamamura, K., Onishi, S., and Shizuta, Y.: Targeted disruption of the aromatase P450 gene (Cyp19) in mice and their ovarian and uterine responses to17b-oestradiol. J. Endocrinol. 170, 99-111 (2001).
62. Takeuchi, O., Kawai, T., Muhlradt, P. F., Morr, M., Radolf, J. D., Zychlinsky, A., Takeda, K., and Akira, S.: Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int. Immunol. 13, 933-940 (2001).
61. Mahalingam, S., Karupiah, G., Takeda, K., Akira, S., Matthaei, K. I., and Foster, P. S.: Enhanced resistance in STAT6-deficient mice to infection with ectromelia virus. Proc. Natl. Acad. Sci. USA. 98, 6812-6817 (2001).
60. Toda, K., Okada, T., Takeda, K., Akira, S., Shiraishi, K., Shinoda, K., Kaname, T., Yamamura, K., and Shizuta, Y.: Oestrogen at the neonatal stage is critical for the reproductive ability of male mice as revealed by supplementation with 17 b-oestradiol to aromatase gene (Cyp19) knockout mice. J. Endocrinol. 168, 455-463 (2001).
59. Matsushima, A., Kaisho, T., Rennert, P. D., Nakano, H., Kurosawa, K., Uchida, D., Takeda, K., Akira, S., and Matsumoto, M.: Essential role of nuclear factor (NF)-kB-inducing kinase and inhibitor of kB (IkB) kinase in NF-kB activation through lymphotoxin-receptor, but not through tumor necrosis factor receptor I. J. Exp. Med. 193, 631-636 (2001).
58. Kaisho, T., Takeda, K., Tsujimura, T., Kawai, T., Nomura, F., Terada, N., and Akira, S.: IkB kinase a is essential for mature B cell development and function. J. Exp. Med. 193, 417-426 (2001).
57. Suzuki, A., Hanada, T., Mitsuyama, K., Yoshida, T., Kamizono, S., Hoshino. T., Kubo, M., Yamashita, A., Okabe, M., Takeda, K., Akira, S., Matsumoto, S., Toyonaga, A., Sata, M., and Yoshimura, A.: CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation. J. Exp. Med. 193, 471-482 (2001).
56. Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Hoshino, K., Wagner, H., Takeda, K., and Akira, S.: A Toll-like receptor recognizes bacterial DNA. Nature 408, 740-745 (2000).
55. Sato, S., Nomura, F., Kawai, T., Takeuchi, O., Muhlradt, P. F., Takeda, K., and Akira, S.: Synergy and cross-tolerance between Toll-like receptor (TLR) 2- and TLR4-mediated signaling pathways. J. Immunol. 165, 7096-7101 (2000).
54. Pien, G. C., Satoskar, A. R., Takeda, K., Akira, S., Biron, C. A.: Selective IL-18 requirements for induction of compartmental IFN-g responses during viral infection. J. Immunol. 165, 4787-4791 (2000).
53. Schnare, M., Holt, A. C., Takeda, K., Akira, S., and Medzhitov, R.: Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Curr. Biol. 10, 1139-1142 (2000).
52. Lu, H., Yang, X., Takeda, K., Zheng, D., Fan, Y., Luo, M., Shen, C., Wang, S., Akira, S., and Brunham, R. C.: Chlamydia trachomatis mouse pneumonitis infection in IL-18 and IL-12 knockout mice: IL-12 is dominant over IL-18 in protective immunity. Mol. Med. 6, 604-612 (2000).
51. Shi, F.-D., Takeda, K., Akira, S., Sarvetnick, N., Ljunggren, H.-G.: IL-18 directs autoreactive T cells and promotes autodestruction in the central nervous system via induction of IFN-g by NK cells. J. Immunol. 165, 3099-3104 (2000).
50. Hashimoto, A., Takeda, K., Inaba, M., Sekimata, M., Kaisho, T., Ikehara, S., Homma, Y., Akira, S., and Kurosaki, T.: Essential role of phospholipase C-g2 in B cell development and function. J. Immunol. 165, 1738-1742 (2000).
49. Sakao, Y., Kawai, T., Takeuchi, O., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Takeda, K., Akira, S.: Mouse proteasomal ATPases Psmc3 and Psmc4: genomic organization and gene targeting. Genomics 67, 1-7 (2000).
48. Hashimoto, M., Imamura, Y., Morichika, T., Arimoto, K., Takeuchi, O., Takeda, K., Akira, S., Aoyama, K., Tamura, T., Kotani, S., Suda, Y., and Kusumoto, S.: Cytokine-inducing macromolecular glycolipids from Enterococcus hirae: Improved method for separation and analysis of its effects on cellular activation. Biochem. Biophys. Res. Commun. 273, 164-169 (2000).
47. Kawakami, K., Koguchi, Y., Qureshi, M. S., Miyazono, 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-g production by NK cells. J. Immunol. 165, 941-947 (2000).
46. Sansonetti, P. J., Phalipon, A., Arondel, J., Thirumalai, A., Banerjee, S., Akira, S., Takeda, K., and Zychlinsky, A.: Caspase-1 activation of IL-1b and IL-18 are essential for Shigella flexneri induced inflammation. Immunity 12, 581-590 (2000).
45. Monteforte, G. M., Takeda, K., Rodriguez-Sosa, M., Akira, S., David, J. R., and Satoskar, A. R.: Genetically resistant mice lacking IL-18 gene develop Th1 response and control cutaneous Leishmania major infection. J. Immunol. 164, 5890-5893 (2000).
44. Kawakami, K., Koguchi, Y., Qureshi, M. H., Kinjo, Y., Yara, S., Miyazato, A., Kurimoto, M., Takeda, K., Akira, S., Saito, A.: Reduced host resistance and Th1 response to Cryptococcus neoformans in interleukin-18 deficient mice. FEMS Microbiol. Lett. 186, 121-126 (2000).
43. Ohkusu, K., Yoshimoto, T., Takeda, K., Ogura, T., Kashiwamura, S., Iwakura, K., 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).
42. Yokozeki, H., Ghoreishi, M., Takagawa, S., Takayama, K., Satoh, T., Katayama, I., Takeda, K., Akira, S., and Nishioka, K.: Signal transducer and activator of transcription 6 is essential in the induction of contact hypersensitivity. J. Exp. Med. 191, 995-1004 (2000).
41. Nomura, F., Akashi, S., Sakao, Y., Sato, S., Kawai, T., Matsumoto, M., Nakanishi, K., Kimoto, M., Miyake, K., Takeda, K., and Akira, S.: Endotoxin tolerance in mouse peritoneal macrophages correlates with downregulation of surface Toll-like receptor 4 expression. J. Immunol. 164, 3476-3479 (2000).
40. Akashi, S., Shimazu, R., Ogata, H., Nagai, Y., Takeda, K., Kimoto, M., and Miyake, K.: Cell surface expression and LPS signaling via the Toll-like receptor 4-MD2 complex on mouse peritoneal macrophages. J. Immunol. 164, 3471-3475 (2000).
39. Kawakami, K., Qureshi, M. H., Zhang, T., Koguchi, Y., Yara, S., Takeda, K., Akira, S., Kurimoto, M., and Saito, A.: Involvement of endogenously synthesized interleukin (IL)-18 in the protective effect of IL-12 against pulmonary infection with Cryptococcus neoformans in mice. FEMS Immunol. Med. Microbiol. 23, 191-200 (2000).
38. Takeuchi, S., Takeda, K., Oishi, I., Nomi, M., Ikeya, M., Itoh, K., Tamura, S., Ueda, T., Hatta, T., Otani, H., Terashima, T., Takada, S., Yamamura, H., Akira, S., and Minami, Y.: Mouse Ror2 receptor tyrosine kinase is required for the heart development and limb formation. Genes Cells 5, 71-78 (2000).
37. Okuda, T., Takeda, K., Fujita, Y., Nishimura, M., Yagyu, S., Yoshida, M., Akira, S., Downing, J. R., and Abe, T.: Biological characteristics of the leukemia-associated transcriptional factor AML1 disclosed by hematopoietic rescue of AML1-deficient embryonic stem cells using a knock-in strategy. Mol. Cell. Biol. 20, 319-328 (2000).
36. Takeuchi, O., Takeda, K., Hoshino, K., Adachi, O., Ogawa, T., and Akira, S. : Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades. Int. Immunol. 12, 113-117 (2000).
35. Hoshino, K., Kashiwamura, S., Kuribayashi, K., Kodama, T., Tsujimura, T., Nakanishi, K., Matsuyama, T., Takeda, K., and Akira, S.: Absence of IL-1 receptor-related T1/ST2 does not affect T helper cell type 2 development and its effector function. J. Exp. Med. 190, 1541-1548 (1999).
34. Kaisho, T., Tsutsui, H., Tanaka, T., Tsujimura, T., Takeda, K., Kawai, T., Yoshida, N., Nakanishi, K., and Akira, S.: Impairment of natural killer cytotoxic activity and interferon-g production in C/EBPg-deficient mice. J. Exp. Med. 190, 1673-1582 (1999).
33. Takeuchi, O., Hoshino, K., Kawai, T., Sanjo, H., Takada, H., Ogawa, T., Takeda, K., and Akira, S.: Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity 11, 443-451 (1999).
32. Chapman, R. S., Lourenco, P., Tonner, E., Flint, D. J., Selbert, S., Takeda, K., Akira, S., Clarke, A. R., and Watson, C. J. : Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3. Genes Dev. 13, 2604-2616 (1999).
31. Sano, S., Itami, S., Takeda, K., Tarutani, M., Yamaguchi, Y., Miura, H., Yoshikawa, K., Akira, S., and Takeda, J. : Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis. EMBO J. 18, 4657-4668 (1999).
30. Tsutsui, H., Kayagaki, N., Kuida, K., Nakano, H., Hayashi, N., Takeda, K., Matsui, K., Kashiwamura, S., Hada, T., Akira, S., Yagita, H., Okamura, H., and Nakanishi, K.: Caspase-1-independent Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice. Immunity 11, 359-367 (1999).
29. Hayashi, N., Matsui, K., Tsutsui, H., Osada, Y., Mohamed, R. T., Kashiwamura, S., Hyodo, Y., Takeda, K., Akira, S., Hada, T., Higashino, K., Kojima, S., and Nakanishi, K. : Kupffer cells from Schistosoma mansoni-infected mice are responsible for prompt type-2-differentiation of hepatic T cells in response to worm antigens. J. Immunol. 163, 6702-6711 (1999).
28. Sugawara, I., Yamada, H., Kaneko, H., Mizuno, S., Takeda, K., and Akira, S.: Role of interleukin-18 (IL-18) in mycobacterial infection in IL-18-gene-disrupted mice. Infect. Immun. 67, 2585-2589 (1999).
27. Shimada, T., Kawai, T., Takeda, K., Matsumoto, M., Inoue, J. ,Tatsumi, Y., Kanamaru, A., and Akira, S. :IKK-i: A novel lipopolysaccharide-inducible kinase that is related to IkB kinase. Int. Immunol. 11, 1357-1362 (1999).
26. Kawai, T., Adachi, O., Ogawa, T., Takeda, K., and Akira, S.: Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11, 115-122 (1999).
25. Takeda, K., Takeuchi, O., Tsujimura, T., Itami, S., Adachi, O., Kawai, T., Sanjo, H., Yoshikawa, K., Terada, N., and Akira, S.: Limb and skin abnormalities in mice lacking IKKa. Science 284, 313-316 (1999).
24. Riley, J. K., Takeda, K., Akira, S., and Schreiber, R. D.: Interleukin-10 receptor signaling through the JAK-STAT pathway: requirement for two distinct receptor derived signals for anti-inflammatory action. J. Biol. Chem. 274, 16513-16521 (1999).
23. Hoshino, K., Tsutsui, H., Kawai, T., Takeda, K., Nakanishi, K., Takeda, Y., and Akira, S.: Generation of IL-18-receptor-deficient mice: evidence for IL-1Rrp as an essential IL-18 binding receptor. J. Immunol. 162, 5041-5044 (1999).
22. Takeuchi, O., Kawai, T., Sanjo, H., Copeland, N. G., Gilbert, D. J., Jenkins, N., Takeda, K., and Akira, S.: TLR6: a novel member of an expanding toll-like receptor family. Gene 231, 59-65 (1999).
21. Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K., and Akira, S.: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to LPS: evidence for TLR4 as the Lps gene product. J. Immunol. 162, 3749-3752 (1999).
20. Miyata, S., Matsuyama, T., Kodama, T., Nishioka, Y., Kuribayashi, K., Takeda, K., Akira, S., and Sugita, M.: STAT6 deficiency in a mouse model of allergen-induced airways inflammation abolishes eosinophilia but induces infiltration of CD8+ T cells. Clin. Exp. Allergy, 29, 114-126 (1999).
19. Takeda, K., Clausen, B., Kaisho, T., Tsujimura, T., Terada, N., Forster, I., and Akira, S.: Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10, 39-49 (1999).
18. Sakao, Y., Takeda, K., Tsutsui, H., Nomura, F., Okamura, H., Nakanishi, K., and Akira, S. : IL-18-deficient mice are resistant to endotoxin-induced liver injury but highly susceptible to endotoxin shock. Int. Immunol. 11, 471-480 (1999).
17. Hyodo, Y., Matsui, K., Hayashi, N., Tsutsui, H., Kashiwamura, S., Yamauchi, H., Hiroishi, K., Takeda, K., Tagawa, Y., Iwakura, Y., Kayagaki, N., Kurimoto, M., Hada, T., Okamura, H., Yagita, H., Akira, S., Nakanishi, K., and Higashino, K.: IL-18 up-regulates perforin-mediated NK activity without increasing perforin messenger RNA expression by binding to constitutively expressed IL-18 receptor. J. Immunol. 162, 1662-1668 (1999).
16. Tanaka, T., Tsujimura, T., Takeda, K., Sugihara A., Maekawa, A., Terada, N., Yoshida, N., and Akira, S.: Targeted disruption of ATF4 discloses its essential role in formation of eye lens secondary fibers. Genes Cells 3, 801-810 (1998).
15. Akaishi, H., Takeda, K., Kaisho, T., Shineha, R., Satomi, S., Takeda, J., and Akira, S.: Defective IL-2-mediated IL-2 receptor a chain expression in Stat3-deficient T lymphocytes. Int. Immunol.,10, 1747-1751 (1998).
14. Yoshimoto, T., Takeda, K., Tanaka, T., Ohkusu, K., Kashiwamura, S., Okamura, H., Akira, S., and Nakanishi, K. : Interleukin 12 up-regulates IL-18 receptor expression on T cells, Th1 cells and B cells: Synergism with IL-18 for IFN-g production. J. Immunol. 161, 3400-3407 (1998).
13. Adachi, O., Kawai, T., Takeda, K., Matsumoto, M., Tsutsui, H., Sakagami, M., Nakanishi, K., and Akira, S.: Targeted disruption of the MyD88 gene resulted in impaired IL-1- and IL-18-mediated function. Immunity, 9, 143-150 (1998)
12. Takeda, K., Kaisho T., Yoshida, N., Takeda, J., Kishimoto, T., and Akira, S.: Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: Generation and characterization of T cell-specific Stat3-deficient mice. J. Immunol, 161, 4652-4660 (1998)
11. Akimoto, T., Numata, F., Tamura, M., Takata, Y., Higashida, N., Takashi, T., Takeda, K., and Akira, S.: Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in STAT6-deficient mice. J. Exp. Med., 187, 1537-1542 (1998)
10. Takeda, K., Tsutsui, H., Yoshimoto, T., Adachi, O., Yoshida, N., Kishimoto, T., Okamura, H., Nakanishi, K., and Akira, S.: Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity, 8, 383-390 (1998)
9. Kawai, T., Matsumoto, M., Takeda, K., Sanjo, H., and Akira, S.: ZIP-kinase, anovel serinr/threonine kinase which mediates apoptosis. Mol. Cell. Biol., 18, 1842-1651 (1998)
8. Takeda, K., Noguchi, K., Shi, W., Tanaka, T., Matsumoto, M., Yoshida, N., Kishimoto, T., and Akira, S.: Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc. Natl. Acad. Sci. USA 94, 3801-3804 (1997)
7. Matsumoto, M., Minami, M., Takeda, K., Sakao, Y., and Akira, S.: Ectopic expressionof CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells. FEBS Letter 395, 143-147 (1996)
6. Takeda, K., Kamanaka, K., Tanaka, T., Kishimoto, T., and Akira, S.: Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice. J. Immunol. 157, 3220-3222 (1996)
5. Shi, W., Inoue, M., Minami, M., Takeda, K., Matsumoto, M., Matsuda, Y., Kishimoto, T., and Akira, S.: The genomic structure and chromosomal localization of the mouse STAT3 gene. Int. Immunol. 8, 1205 (1996)
4. Takeda, K., Tanaka,T., Shi, W., Matsumoto, M., Minami, M., Kashiwamura, S., Nakanishi, K., Yoshida, N., Kishimoto, T., and Akira, S.: Essential role of Stat6 in IL-4 signalling. Nature 380, 627-630 (1996).
3. Minami, M., Inoue, M., Shi, W., Takeda, K., Matsumoto, M., Kishimoto, T., and Akira, S.: STAT3 activation is a critical step in gp130-mediated terminal differentiation and growth arrest of a myeloid cell line. Proc. Natl. Acad. USA. 93, 3963-3966 (1996).
2. Sawada, M., Nagamine, J., Takeda, K., Utsumi, K., Kosugi, A., Tatsumi, Y., Hamaoka, T., Miyake, K., Nakajima, K., Watanabe, T., Sakakibara, S., and Fujiwara, H.: Expression of VLA-4 on thymocytes. maturation stage-associated transition and its correlation with their capacity to adhere to thymic stromal cells. J. Immunol. 149, 3517-3524 (1992).
1. Nagamine, J., Takeda, K., Tatsumi, Y., Ogata, M., Miyake, K., Hamaoka, T., and Fujiwara, H.: Role of a thymic stromal cell clone in inducing the stage-specific differentiation of various subpopulations of double negative thymocytes. J. Immunol. 147, 1147-1152 (1991).
