Elucidation of recognition and response of intestinal immune cells to microbes in relation to development of immunomodulating functional foods

2013 Fiscal Year Final Research Report

• Project/Area Number: 23380073
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: The University of Tokyo
• Principal Investigator: HACHIMURA SATOSHI 東京大学, 農学生命科学研究科, 准教授 (40238019)
• Co-Investigator(Kenkyū-buntansha): NAKAYAMA Jiro 九州大学, 農学研究院, 准教授 (40217930) ; TAKAHASHI Yoshimasa 国立感染症研究所, 免疫部, 室長 (60311403) ; HOSONO Akira 日本大学, 生物資源科学部, 准教授 (70328706)
• Research Collaborator: NAKAJIMA Haruyo (ADACHI Haruyo) 東京大学, 農学生命科学研究科, 特任研究員 (20595962)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 腸管免疫系 / 腸内共生菌 / 機能性食品 / IgA抗体 / TLR / 制御性T細胞 / 樹状細胞 / 経口免疫寛容

Research Abstract

In this study, we tried to elucidate the functions of intestinal immune cells, focusing on their responses to microbes and microbial components, in relation to development of novel immunomodulating functional foods. We examined the suppressive response of Peyer's patch dendritic cells to multiple TLR simulation. We analyzed CD3-IL-2R+ cells, and found that they were also present in the lungs, and that they responded to influenza virus infection. We also examined gene expression of regulatory T cells induced in oral tolerance. Furthermore, we examined the mechanism of IgA induction by Bacteroides.

Research Products

• [Journal Article] Attenuation of migration properties of CD4+ T cells from aged mice correlates with decrease in chemokine receptor expression, response to retinoic acid and RALDH expression compared to young mice (2014)
  • Author(s): Park, J., Miyakawa, T., Shiokawa, A., Nakajima-Adachi, H., Tanokura, M., Hachimura, S
  • Journal Title: Biosci. Biotechnol. Biochem. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Oral Administration of Lactobacillus plantarum Strain AYA Enhances IgA Secretion and Provides Survival Protection against Influenza Virus Infection in Mice (2014)
  • Author(s): Kikuchi, Y., Kunitoh-Asari, A., Hayakawa, K., Imai, S., Kasuya, K., Abe, K., Adachi, Y., Fukudome, S., Takahashi, Y., Hachimura, S
  • Journal Title: PLoS ONE Volume: 9, e86416
  • DOI: 10.1371/journal.pone.00864
  • Peer Reviewed
• [Journal Article] Generation of memory B cells inside and outside germinal centers (2014)
  • Author(s): Takemori, T., Kaji, T., Takahashi, Y., Shimoda, M., Rajewsky, K
  • Journal Title: Eur. J. Immunol Volume: 44 Pages: 1258-1264
  • DOI: 10.1002/eji.201343716
• [Journal Article] Enhancement of intestinal immune function in mice by β-D-glucan from aureobasidium pullulans ADK-34 (2013)
  • Author(s): Tanioka, A., Tanabe, K., Hosono, A., Kawakami, H., Kaminogawa, S., Tsubaki, K., Hachimura, S
  • Journal Title: Scand. J. Immunol Volume: 78 Pages: 61-8
  • DOI: 10.1111/sji.12067
  • Peer Reviewed
• [Journal Article] Both unmutated and mutated memory B cells accumulate mutations and renew antibody repertoire optimally adopted to antigen upon re-exposure (2013)
  • Author(s): Kaji, T., Furukawa, K., Ishige, A., Toyokura, I., Takahashi, Y., Shimoda, M., Takemori, T
  • Journal Title: Int. Immunol Volume: 25 Pages: 683-695
  • DOI: 10.1093/intimm/dxt030
  • Peer Reviewed
• [Journal Article] Influenza A whole virion vaccine induces a rapid reduction of peripheral blood leukocytes via interferon-alpha-dependent apoptosis (2013)
  • Author(s): Ato, M., Takahashi, Y., Fujii, H., Hashimoto, S., Kaji, T., Itamura, S., Horiuchi, Y., Arakawa, Y., Tashiro, M., Takemori, T
  • Journal Title: Vaccine Volume: 31 Pages: 2184-2190
  • DOI: 10.1016/j.vaccine.2013.02.016
  • Peer Reviewed
• [Journal Article] IgA production in the large intestine is modulated by a different mechanism than in the small intestine : Bacteroides acidifaciens promotes IgA production in the large intestine by inducing germinal center formation and increasing the number of IgA^<+> B cells (2013)
  • Author(s): Yanagibashi,T., Hosono, A., Oyama, A., Tsuda, M., Suzuki, A., Hachimura, S., Takahashi, Y., Momose, Y., Itoh, K., Hirayama, K., Takahashi, K., Kaminogawa, S
  • Journal Title: Immunobiology Volume: 218 Pages: 645-651
  • DOI: 10.1016/j.imbio.2012.07.033
  • Peer Reviewed
• [Journal Article] Distinct cellular pathways select germ-line encoded and somatically mutated antibodies into immunological memory (2012)
  • Author(s): Kaji, T., Ishige, A., Hikida, M., Taka, J., Hijikata, A., Kubo, M., Nagashima, T., Takahashi, Y., Kurosaki, T., Okada, M., Ohara, O., Rajewsky, K., Takemori, T
  • Journal Title: J. Exp. Med Volume: 209 Pages: 2079-2097
  • DOI: 10.1084/jem.20120127
  • Peer Reviewed
• [Journal Article] 腸管におけるIgA 産生とCD3^<->IL-2R^<+>細胞 (2012)
  • Author(s): 八村敏志
  • Journal Title: 臨床免疫・アレルギー科 Volume: 58 Pages: 387-390
• [Journal Article] Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection (2012)
  • Author(s): Onodera, T., Takahashi, Y., Yokoi, Y., Ato, M., Kodama, Y., Hachimura, S., Kurosaki, T., Kobayashi, K
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 109 Pages: 2485-2490
  • DOI: 10.1073/pnas.1115369109
  • Peer Reviewed
• [Journal Article] Commensal bacteria promote migration of mast cells into the intestine (2011)
  • Author(s): Kunii, J., Takahashi, K., Kasakura, K., Tsuda, M., Nakano, K., Hosono, A., Kaminogawa, S
  • Journal Title: Immunobiology Volume: 216 Pages: 692-697
  • DOI: 10.1016/j.imbio.2010.10.007
  • Peer Reviewed
• [Journal Article] Transcription of the Tollip gene is elevated in intestinal epithelial cells through impaired O-GlcNAcylation-dependent nuclear translocation of the negative regulator Elf-1 (2011)
  • Author(s): Sugi, Y., Takahashi, K., Nakano, K., Hosono, A., Kaminogawa, S
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 412 Pages: 704-709
  • DOI: 10.1016/j.bbrc.2011.08.035
  • Peer Reviewed
• [Journal Article] Epigenetic control of the host gene by commensal bacteria in large intestinal epithelial cells (2011)
  • Author(s): Takahashi, K., Sugi, Y., Nakano, K., Tsuda, M., Kurihara, K., Hosono, A., Kaminogawa, S
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 35755-35762
  • DOI: 10.1074/jbc.M111.271007
  • Peer Reviewed
• [Journal Article] Gut as a target for functional food (2011)
  • Author(s): Shimizu, M., Hachimura, S
  • Journal Title: Trend. Food Sci. Technol Volume: 22 Pages: 646-650
  • DOI: 10.1016/j.tifs.2011.06.002
• [Journal Article] ウイルス感染局所における記憶B 細胞応答 (2011)
  • Author(s): 高橋宜聖, 小野寺大志, 小林和夫
  • Journal Title: 実験医学増刊 Volume: 29 Pages: 81-86
• [Journal Article] 腸管自然免疫系と腸内細菌
  • Author(s): 八村敏志
  • Journal Title: 臨床栄養 Volume: 120 Pages: 685-685-688
• [Presentation] 加齢による免疫機能変化と食品による調節 (2014)
  • Author(s): 八村敏志, 田之倉優
  • Organizer: 日本農芸化学会2014年度大会
  • Place of Presentation: 明治大学(神奈川)
  • Year and Date: 2014-03-30
• [Presentation] 経口免疫寛容において誘導されるCD62L^<high/int>CD44^<int> およびCD62L^<low>CD44^<high>T 細胞の機能解析 (2014)
  • Author(s): 芝原恭子ら
  • Organizer: 日本農芸化学会2014年度大会
  • Place of Presentation: 明治大学(神奈川)
  • Year and Date: 2014-03-28
• [Presentation] 腸内細菌による腸管免疫細胞の制御 : アレルギー抑制に関連して (2014)
  • Author(s): 八村敏志
  • Organizer: 第17回日本病態栄養学会年次学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2014-01-12
• [Presentation] Suppression of TLR9-induced response by TLR2 pathway in Peyer's patch dendritic cells (2013)
  • Author(s): KOTAKI Ryutaro ら
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2013-12-12
• [Presentation] 粘膜組織に存在するIgA産生促進CD3-IL-2R+細胞のユニークな性状 (2012)
  • Author(s): 横井勇祐ら
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都女子大学(京都)
  • Year and Date: 2012-03-24
• [Presentation] 腸内共生菌のIgA 産生に関わる免疫担当細胞に対する作用 (2011)
  • Author(s): 石井俊祐ら
  • Organizer: 日本食品免疫学会2011年度大会
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2011-10-18
• [Presentation] 複数のTLR 刺激を受けたパイエル板樹状細胞における応答抑制の解析 (2011)
  • Author(s): 上滝隆太郎ら
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 東北大学(宮城)
  • Year and Date: 2011-03-25