Role of Innate Immunity in self/nonself discrimination

2011 Fiscal Year Final Research Report

• Project Area: Immunological Self Recognition and its Disorders
• Project/Area Number: 19059011
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: TAKEDA Kiyoshi 大阪大学, 医学系研究科, 教授 (20309446)
• Project Period (FY): 2007 – 2011
• Keywords: 自然免疫 / 遺伝子発現 / 粘膜免疫

Research Abstract

We analyzed the mechanisms by which discrimination of self and non-self via pattern recognition receptors regulates innate immune responses. First, we revealed that nuclear factor IκBζ regulates gene expression induced by pattern recognition receptors. We also analyzed the regulatory mechanisms of intestinal innate immune cells by commensal microflora, which are non-self but not recognized as non-self. We revealed that activity of intestinal macrophages is negatively regulated by commensal microflora. We also demonstrated that a commensal bacteria-derived factor activates intestinal dendritic cells to induce T cell-dependent responses.

Research Products

• [Journal Article] Intestinal CX_3C chemokine receptor 1^<high> (CX_3CR1^<high>) myeloid cells prevent T cell-dependent colitis (2012)
  • Author(s): Kayama, H., Ueda, Y., Sawa, Y., Jeon, S. G., Ma, J. S., Okumura, R., Kubo, A., Ishii, M., Okazaki, T., Murakami, M., Yamamoto, M., Yagita, H. and Takeda, K.
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 109 Pages: 5010-5015
  • Peer Reviewed
• [Journal Article] Inhibition of ATF6β-dependent host adaptive immune response by a Toxoplasma virulence factor ROP18 (2012)
  • Author(s): Yamamoto, M. and Takeda, K.
  • Journal Title: Virulence Volume: 3 Pages: 77-80
  • Peer Reviewed
• [Journal Article] ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18 (2011)
  • Author(s): Yamamoto, M., Ma, J. S., Mueller, C., Kamiyama, N., Saiga, H., Kubo, E., Kimura, T., Okamoto, T., Okuyama, M., Kayama, H., Nagamune, K., Takashima, S., Matsuura, Y., Soldati-Farve, D. and Takeda, K.
  • Journal Title: J. Exp. Med. Volume: 208 Pages: 1533-1546
  • Peer Reviewed
• [Journal Article] Induction of colonic regulatory T cells by indigenous Clostridium species (2011)
  • Author(s): Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., Taniguchi, T., Takeda, K., Hori, S., Ivanov, I.I., Umesaki, Y., Itoh, K., and Honda, K.
  • Journal Title: Science Volume: 331 Pages: 337-341
  • Peer Reviewed
• [Journal Article] Commensal microbiota induce LPS hyporesponsiveness in colonic macrophages via the production of IL-10 (2010)
  • Author(s): Ueda, Y., Kayama, H., Jeon, S.-G., Kusu, T., Isaka, Y., Rakugi, H., Yamamoto, M. and Takeda, K.
  • Journal Title: Int. Immunol. Volume: 22 Pages: 953-962
  • Peer Reviewed
• [Journal Article] The innate immune response to Trypanosoma cruzi infection (2010)
  • Author(s): Kayama, H. and Takeda, K.
  • Journal Title: Microbes Infect. Volume: 12 Pages: 511-517
  • Peer Reviewed
• [Journal Article] A novel inducible dendritic cell ablation model in mice (2010)
  • Author(s): Okuyama, M., Kayama, H., Atarashi, K., Saiga, H., Kimura, T., Waisman, A., Yamamoto, M., and Takeda, K.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 397 Pages: 559-563
  • Peer Reviewed
• [Journal Article] A single polymorphic amino acid on Toxoplasma gondii kinase ROP16 determines the direct and strain-specific activation of Stat3 (2009)
  • Author(s): Yamamoto, M., Standley, D.M., Takashima, S., Saiga, H., Okuyama, M., Kayama, H., Kubo, E., Ito, H., Takaura, M., Matsuda, T., Soldati-Farve, D., and Takeda, K.
  • Journal Title: J. Exp.Med. Volume: 206 Pages: 2747-2760
  • Peer Reviewed
• [Journal Article] The lipid A receptor (2009)
  • Author(s): Takeda, K.
  • Journal Title: Lipid A in cancer therapy Pages: 53-58
  • Peer Reviewed
• [Journal Article] :Induction of Intestinal Th17 cells bysegmented filamentous bacteria (2009)
  • Author(s): Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., Tanoue, T., Imaoka, A., Itoh, K., Takeda, K., Umesaki, Y., Honda, K., Littman, D. R.
  • Journal Title: Cell Volume: 139 Pages: 485-498
  • Peer Reviewed
• [Journal Article] NFATc1 mediates Toll-like receptor-independent innate immune responses during Trypanosoma cruzi infection (2009)
  • Author(s): Kayama, H., Koga, R., Atarashi, K., Mak, T. W., Takayanagi, H., Honda, K., Yamamoto, M. and Takeda, K.
  • Journal Title: PLoS Pathogens Volume: 5 Pages: e1000514
  • Peer Reviewed
• [Journal Article] C-type lectin Mincle is an activating receptor for pathogenic fungus (2009)
  • Author(s): Yamasaki, S., Matsumoto, M., Takeuchi, O., Matsuzawa, T., Ishikawa, E., Sakuma, M., Takeno, H., Uno, J., Hirabayashi, J., Mikami, Y., Takeda, K., Akira, S., and Saito, T.
  • Journal Title: Malassezia. Proc. Natl. Acad. Sci. USA. Volume: 106 Pages: 1897-1902
  • Peer Reviewed
• [Journal Article] Fra-1 negatively regulates lipopolysaccharide-mediated inflammatory responses (2009)
  • Author(s): Morishita, H., Saito, F., Kayama, H., Atarashi, K., Kuwata, H., Yamamoto, M., and Takeda, K.
  • Journal Title: Int. Immunol. Volume: 21 Pages: 457-465
  • Peer Reviewed
• [Journal Article] Regulatory mechanisms of immune responses to intestinal bacteria (2009)
  • Author(s): Honda, K., and Takeda, K.
  • Journal Title: Mucosal Immunol. Volume: 2 Pages: 187-196
  • Peer Reviewed
• [Journal Article] Lipocalin 2-dependent inhibition of mycobacterial growth in alveolar epithelium (2008)
  • Author(s): Saiga, H., Nishimura, J., Kuwata, H., Okuyama, M., Matsumoto, S., Sato, S., Matsumoto, M., Akira, S., Yoshikai, Y., Honda, K., Yamamoto, M. and Takeda, K.
  • Journal Title: J. Immunol. Volume: 181 Pages: 8521-8527
  • Peer Reviewed
• [Journal Article] ATP drives lamina propria TH17 cell differentiation (2008)
  • Author(s): Atarashi, K., Nishimura, J., Shima, T., Umesaki, Y., Yamamoto, M., Onoue, M., Yagita, H., Ishii, N., Evans, R., Honda, K., and Takeda, K.
  • Journal Title: Nature Volume: 455 Pages: 808-812
  • Peer Reviewed
• [Journal Article] Role of nuclear IkB proteins in the regulation of host immune responses (2008)
  • Author(s): Yamamoto, M., and Takeda, K.
  • Journal Title: J. Infect. Chemother Volume: 14 Pages: 265-269
  • Peer Reviewed
• [Journal Article] Inefficient phagosome maturation in infant macrophages (2008)
  • Author(s): Saito, F., Kuwata, H., Oike, E., Koike, M., Uchiyama, Y., Honda, K., and Takeda, K.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 375 Pages: 113-118
  • Peer Reviewed
• [Journal Article] Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IκBζ (2008)
  • Author(s): Kayama, H., Ramirez-Carrozzi, V. R., Yamamoto, M., Mizutani, T., Kuwata, H., Iba, H., Matsumoto, M., Honda, K., Smale, S. T., and Takeda, K.
  • Journal Title: J. Biol. Chem. Volume: 283 Pages: 12468-12477
  • Peer Reviewed
• [Journal Article] Potent antimycobacterial activity of mouse secretory leukocyte protease inhibitor (2008)
  • Author(s): Nishimura, J., Saiga, H., Sato, S., Okuyama, M., Kayama, H., Kuwata, H., Matsumoto, S., Nishida, T., Sawa, Y., Akira, S., Yoshikai, Y., Yamamoto, M., and Takeda, K.
  • Journal Title: J. Immunol. Volume: 180 Pages: 4032-4039
  • Peer Reviewed
• [Journal Article] Assessing the response of cells to TLR stimulation (2008)
  • Author(s): Takeda, K., Yamamoto, M., Honda, K.
  • Journal Title: Signaling by Toll-like receptors Pages: 1-21
  • Peer Reviewed
• [Journal Article] Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency (2007)
  • Author(s): Yamamoto, M., Uematsu, S., Okamoto, T., Matsuura, Y., Sato, S., Kumar, H., Satoh, T., Saitoh, T., Takeda, K., Ishii, K. J., Takeuchi, O., Kawai, T., and Akira, S.
  • Journal Title: J. Exp. Med. Volume: 204 Pages: 2233-2239
  • Peer Reviewed
• [Presentation] Regulatory Mechanisms of Immune Responses to Intestinal Bacteria (2012)
  • Author(s): Kiyoshi Takeda, Hisako Kayama
  • Organizer: Keystone Symposium
  • Place of Presentation: Keystone, USA
  • Year and Date: 20120304-08
• [Presentation] Regulation of gut homeostasis by microbiota and innate immunity (2012)
  • Author(s): Kiyoshi Takeda
  • Organizer: The 4^<th> Symposium of Immunological Self.
  • Place of Presentation: Kyoto
  • Year and Date: 20120127-28
• [Presentation] Regulation of gut homeostasis by microbiota and innate immunity (2011)
  • Author(s): Kiyoshi Takeda
  • Organizer: Joint Symposium of CRCID, IFReC & IBB
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20111219-20
• [Presentation] A unique subset of intestinal myeloid cells suppress T cell-dependent intestinal inflammation (2011)
  • Author(s): Kiyoshi Takeda, Hisako Kayama
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉(シンポジウム)
  • Year and Date: 20111127-29
• [Presentation] Regulation of intestinal homeostasis by innate immunity (2011)
  • Author(s): Kiyoshi Takeda
  • Organizer: 日本食品免疫学会第7回学術大会
  • Place of Presentation: 東京
  • Year and Date: 20111018-19
• [Presentation] 自然免疫と炎症性疾患 (2011)
  • Author(s): 竹田潔
  • Organizer: 第48回日本眼感染症学会
  • Place of Presentation: 京都
  • Year and Date: 20110708-10
• [Presentation] Regulation of intestinal homeostasis by innate immunity. (2011)
  • Author(s): Kiyoshi Takeda
  • Organizer: The NZ Australian Society for Immunology Branch Meeting 2011
  • Place of Presentation: Welington New Zealand
  • Year and Date: 20110630-0701
• [Presentation] Regulation of intestinal homeostasis by innate immunity (2011)
  • Author(s): Kiyoshi Takeda
  • Organizer: ESF-JSPS Frontier Science Conference for Young Researchers
  • Place of Presentation: Hulshort, The Netherlands
  • Year and Date: 20110301-06
• [Presentation] Innate immune responses at the intestinal mucosa (2010)
  • Author(s): Kiyoshi Takeda
  • Organizer: Annual Meeting of The Society for Leukocyte Biology & The International Endotoxin and Innate Immunity Society
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20101007-09
• [Presentation] Regulation of innate immune responses at the intestinal mucosa (2010)
  • Author(s): Kiyoshi Takeda, Hisako Kayama
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20100822-27
• [Presentation] Regulation of innate immune vresponses at the, intestinal mucosa (2010)
  • Author(s): Kiyoshi Takeda
  • Organizer: Host-Pathogen interactions in generalized bacterial infection
  • Place of Presentation: Greifswald, Germany
  • Year and Date: 20100531-0603
• [Presentation] Regulation of intestinal homeostasis by innate immunity (2010)
  • Author(s): Kiyoshi Takeda
  • Organizer: 第83回日本細菌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20100327-29
• [Presentation] 腸管粘膜に特有の自然免疫系細胞の機能 (2009)
  • Author(s): 竹田潔
  • Organizer: 第39回日本免疫学会学術集会
  • Place of Presentation: 大阪(ランチョンセミナー)
  • Year and Date: 20091202-04
• [Presentation] 自然免疫系の活性制御と免疫疾患 (2009)
  • Author(s): 竹田潔
  • Organizer: 第51回日本小児血液学会
  • Place of Presentation: 東京(特別講演)
  • Year and Date: 20091127-29
• [Presentation] Innate immune responses at the intestinal mucosa (2009)
  • Author(s): Kiyoshi Takeda
  • Organizer: The 2009 Fall Conference of the Korean Association of Immunologists
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20091109-10
• [Presentation] Innate immune responses at the intestinal mucosa (2009)
  • Author(s): Kiyoshi Takeda
  • Organizer: The first CSI/JSI/KAI Join Symposium on Immunology
  • Place of Presentation: Shanghai, China
  • Year and Date: 20091107-08
• [Presentation] トリパノソーマ原虫に対する自然免疫応答機構 (2009)
  • Author(s): 竹田潔
  • Organizer: 第20回日本生体防御学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 20090725-26
• [Presentation] Commensal bacteria-derived ATP mediates development of intestinal Th17 cells (2009)
  • Author(s): Kiyoshi Takeda
  • Organizer: RCAI-JSI International Symposium on Immunology 2009
  • Place of Presentation: 横浜
  • Year and Date: 20090709-10
• [Presentation] NFAT is responsible for TLR-independent innate immune responses to a protozoan parasite (2008)
  • Author(s): Kiyoshi Takeda, Hisako Kayama, Masahiro Yamamoto
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20081209-12
• [Presentation] A mechanism for development of intestinal Th17 cells causing intestinal inflammation (2008)
  • Author(s): Kiyoshi Takeda, Koji Atarashi, Kenya Honda
  • Organizer: The 7^<th> Sino-Japan Joint Conference for Cancer Research
  • Place of Presentation: Guangzhou, China
  • Year and Date: 20081207-10
• [Presentation] Commensal bacteria-derived ATP mediates Th17 cell development in the intestinal lamina propria (2008)
  • Author(s): Kiyoshi Takeda, Koji Atarashi, Kenya Honda
  • Organizer: 第37回日本免疫学会学術集会
  • Place of Presentation: 京都(Symposium)
  • Year and Date: 20081201-03
• [Presentation] 自然免疫系と炎症性腸疾患 (2008)
  • Author(s): 竹田潔
  • Organizer: 第29回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-09
• [Presentation] Regulatory mechanisms of innate immune responses (2008)
  • Author(s): Kiyoshi Takeda
  • Organizer: The Kick-off Symposium on the MEXT Priority Research for Immunological Self
  • Place of Presentation: Kyoto
  • Year and Date: 2008-02-28
• [Presentation] Regulation of innate immune responses (2007)
  • Author(s): Kiyoshi Takeda
  • Organizer: The 9^<th> International Colooquium on Paratuberculosis
  • Place of Presentation: Tsukuba, Japan
  • Year and Date: 2007-10-29
• [Presentation] Regulation of inflammatory responses by nuclear IkB proteins (2007)
  • Author(s): Kiyoshi Takeda
  • Organizer: 8th International Society of Exercise and Immunology Symposium
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2007-10-25
• [Presentation] 自然免疫シグナルの制御機構 (2007)
  • Author(s): 竹田潔
  • Organizer: 第28回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2007-08-02
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/ongene/
• [Patent(Industrial Property Rights)] Ｔ細胞活性化を抑制する腸粘膜特有のミエロイド細胞およびその利用 (2009)
  • Inventor(s): 香山尚子、竹田潔
  • Industrial Property Rights Holder: 大阪大学、科学技術振興機構
  • Industrial Property Number: 特許, 特願 2009-241034
  • Filing Date: 2009-10-20