Analysis on immune regulation by a bacterial quorum sensing molecule

• Project/Area Number: 24390120
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: TAKEDA Kiyoshi 大阪大学, 医学(系)研究科(研究院), 教授 (20309446)
• Co-Investigator(Renkei-kenkyūsha): YOSHIDA Masaru 神戸大学, 医学系研究科, 准教授 (00419475)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 腸内環境 / 上皮 / 炎症 / 腸内細菌 / 免疫 / 免疫学 / 粘膜免疫 / 上皮細胞 / 腸管炎症

Outline of Final Research Achievements

Microbiota have a great influence on barrier functions of intestinal epithelial cells (ECs). The role of indole as a quorum-sensing molecule mediating intercellular signals in bacteria has been well characterized. We analyzed the effect of indole on ECs using a germ free (GF) mouse model. The feces of specific pathogen-free (SPF) mice contained a high amount of indole; however the amount was markedly decreased in the feces of GF mice. GF mice showed decreased expression of junctional complex molecules in colonic ECs. Oral administration of indole-containing capsules resulted in increased expression of both tight junction - and adherens junction-associated molecules in colonic ECs in GF mice. In accordance with the increased expression of these junctional complex molecules, GF mice given indole-containing capsules showed higher resistance to dextran sodium sulfate-induced colitis. These findings demonstrate the beneficial role of indole in establishing an epithelial barrier in vivo.

Research Products

• [Journal Article] The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells. (2015)
  • Author(s): Tsai, S-H., Kinoshita, M., Kusu, T., Kayama, H., Okumura, R., Ikeda, K., Shimada, Y., Takeda, A., Yoshikawa, S., Obata-Ninomiya, K., Kurashima, Y., Sato, S., Umemoto, E., Kiyono, H., Karasuyama, H. and Takeda, K.
  • Journal Title: Immunity Volume: 42(2) Issue: 2 Pages: 279-293
  • DOI: 10.1016/j.immuni.2015.01.015
  • Peer Reviewed / Open Access
• [Journal Article] Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation. (2014)
  • Author(s): Mastumoto, M., Baba, A., Yokota, T., Nishikawa, H., Ohkawa, Y., Kayama, H., Kallies, A., Nut, S. L., Sakaguchi, S., Takeda, K., Kurosaki, T., and Baba, Y.
  • Journal Title: Immunity Volume: 41 Issue: 6 Pages: 1040-1051
  • DOI: 10.1016/j.immuni.2014.10.016
  • Peer Reviewed / Open Access
• [Journal Article] Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA6 (2014)
  • Author(s): Ji Su Ma, Miwa Sasai, Jun Ohshima, Youngae Lee, Hironori Bando, Kiyoshi Takeda, and Masahiro Yamamoto
  • Journal Title: The Journal of Experimental Medicine Volume: 211 Issue: 10 Pages: 2013-2032
  • DOI: 10.1084/jem.20131272
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Generation of colonic IgA-secreting cells in the cecal patch (2014)
  • Author(s): Masahata, K., Umemoto, E., Kayama, H., Kotani, M., Nakamura, S., Kurakawa, T., Kikuta, J., Gotoh, K., Motooka, D., Sato, S., Higuchi, T., Baba, Y., Kurosaki, T., Kinoshita, M., Shimada, Y., Kimura, T., Okumura, R., Takeda, A., Tajima, M., Yoshie, O., Fukuzawa, M., Kiyono, H., Fagarasan, S., Iida, T., Ishii, M., Takeda, K
  • Journal Title: Nature Comm Volume: 5 Issue: 1 Pages: 3704-3704
  • DOI: 10.1038/ncomms4704
  • Peer Reviewed / Open Access
• [Journal Article] A viral RNA structural element alters host recognition of nonself RNA (2014)
  • Author(s): Hyde JL1, Gardner CL, Kimura T, White JP, Liu G, Trobaugh DW, Huang C, Tonelli M, Paessler S, Takeda K, Klimstra WB, Amarasinghe GK, Diamond MS.
  • Journal Title: Science Volume: 343 Issue: 6172 Pages: 783-787
  • DOI: 10.1126/science.1248465
  • Peer Reviewed
• [Journal Article] Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon. (2013)
  • Author(s): Shimada Y1, Kinoshita M, Harada K, Mizutani M, Masahata K, Kayama H, Takeda K.
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e80604-e80604
  • DOI: 10.1371/journal.pone.0080604
  • Peer Reviewed
• [Journal Article] Increased Th17-inducing activity of CD14+ CD163low myeloid cells in intestinal lamina propria of patients with Crohn's disease. (2013)
  • Author(s): Ogino T, Nishimura J, Barman S, Kayama H, Uematsu S, Okuzaki D, Osawa H, Haraguchi N, Uemura M, Hata T, Takemasa I, Mizushima T, Yamamoto H, Takeda K, Doki Y, Mori M.
  • Journal Title: Gastroenterology Volume: 145(6) Issue: 6 Pages: 1380-1391
  • DOI: 10.1053/j.gastro.2013.08.049
  • Peer Reviewed
• [Journal Article] Ifit1 inhibits Japanese encephalitis virus replication through binding to 5' capped 2'-O unmethylated RNA. (2013)
  • Author(s): Kimura T, Katoh H, Kayama H, Saiga H, Okuyama M, Okamoto T, Umemoto E, Matsuura Y, Yamamoto M, Takeda K
  • Journal Title: J. Virology Volume: 87 Issue: 18 Pages: 9997-10003
  • DOI: 10.1128/jvi.00883-13
  • Peer Reviewed
• [Journal Article] CREBH determines the severity of sulpyrine- induced fatal shock. (2013)
  • Author(s): Kamiyama, N, et al
  • Journal Title: PLoS One Volume: 8 Issue: 2 Pages: e55800-e55800
  • DOI: 10.1371/journal.pone.0055800
  • Peer Reviewed
• [Journal Article] ENTPDase7 controls Th17 cell responses through regulation of luminal ATP in the small intestine. (2013)
  • Author(s): Kusu, T., et al.
  • Journal Title: J. Immunol. Volume: 190 Issue: 2 Pages: 774-783
  • DOI: 10.4049/jimmunol.1103067
  • Peer Reviewed
• [Journal Article] Critical role of AIM2 in Mycobacterium tuberculosis infection. (2012)
  • Author(s): Saiga H, et al
  • Journal Title: Int. Immunol. Volume: 24 Issue: 10 Pages: 637-644
  • DOI: 10.1093/intimm/dxs062
  • Peer Reviewed
• [Journal Article] A cluster of IFN-γ-inducible p65 GTPases plays a critical role in host defense against Ibxoplasma gondii (2012)
  • Author(s): Yamamoto M, et al
  • Journal Title: Immunity Volume: 37 Issue: 2 Pages: 302-313
  • DOI: 10.1016/j.immuni.2012.06.009
  • Peer Reviewed
• [Journal Article] Dietary folic Acid promotes survival of foxp3+ regulatory T cells in the colon (2012)
  • Author(s): Kinoshita, M.
  • Journal Title: J. Immunol Volume: 189 Issue: 6 Pages: 2869-2878
  • DOI: 10.4049/jimmunol.1200420
  • Peer Reviewed
• [Presentation] Regulation of antibody responses in the appendix (2015)
  • Author(s): Takeda, K.
  • Organizer: 2nd Hengstbergewr Symposium on “Microbial sensors in the B lymphocyte response”
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 2015-01-07
  • Invited
• [Presentation] 腸内細菌の免疫系や疾患との関わり (2014)
  • Author(s): Takeda, K.
  • Organizer: 42nd JSI Annual Meeting
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
  • Invited
• [Presentation] A mechanism for the host-bacterial segregation in the colon (2014)
  • Author(s): Takeda, K.
  • Organizer: The 1st International Symposium on Mucosal Immunity and Vaccine Development
  • Place of Presentation: Tokyo
  • Year and Date: 2014-10-20 – 2014-10-21
  • Invited
• [Presentation] 消化管粘膜の免疫応答機構とその異常 (2014)
  • Author(s): Takeda, K.
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-26
  • Invited
• [Presentation] 腸管炎症の制御機構の解析 (2014)
  • Author(s): Takeda, K.
  • Organizer: 第29回日本乾癬学会
  • Place of Presentation: 高知
  • Year and Date: 2014-09-19 – 2014-09-21
  • Invited
• [Presentation] Probiotics and innate immunity : Implication for chronic disease prevention (2012)
  • Author(s): Takeda, K
  • Organizer: 5_<th>India Probiotics Symposium
  • Place of Presentation: Bangalore, India(招待講演)
• [Presentation] Regulation of intestinal homeostasis by innate immunity (2012)
  • Author(s): Takeda, K
  • Organizer: The 4_<th> AsiaHORCs Joint Symposium
  • Place of Presentation: Buyeo, Korea
• [Presentation] Regulation of gut homeostasis by innate immunity (2012)
  • Author(s): Takeda, K
  • Organizer: International Endotoxin & Innate Immunity Society Meeting 2012
  • Place of Presentation: 東京
• [Remarks]
  • URL: http://www.mwd.osaka-u.ac.jp/pub/ongene/