Differentiation and function of M cells, a specialized intestinal epithelial cell type, in the mucosal immune system

2008 Fiscal Year Final Research Report

• Project/Area Number: 19390143
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: 大野 博司 The Institute of Physical and Chemical Research, 免疫系構築研究チーム, チームリーダー (50233226)
• Project Period (FY): 2007 – 2008
• Keywords: 免疫学 / 細胞・組織 / M細胞 / 分化 / 抗原取り込み

Research Abstract

パイエル板にはD11c^+CCR6^+のユニークなB細胞が存在し、パイエル板を覆う腸管上皮細胞が分泌するCCR6のリガンドCCL20の作用によりこの細胞が上皮直下へと郵送して上皮と相互作用することによりM細胞が誘導されることが示唆された。
また、M細胞同士はtunneling nanotube (TNT)と呼ばれる細い細胞膜のチューブで連結されているが、われわれはTNT形成因子M-Secを発見し、M-Secがアクチン・リモデリングに働く低分子量GTPaseのRalA/Bや膜輸送の制御因子であるexocyst複合体と相互作用することによりTNT形成を制御していることを明らかにした。

Research Products

• [Journal Article] Mechanism of NKT cell activation by intranasal coadministration of a-galactosylceramide, which can induce cross-protection against influenza (2008)
  • Author(s): Kamijuku, H., Nagata, Y., Jiang, X., Ichinohe, T., Tashiro, T., Mori, K., Taniguchi, M., Hase, K., Ohno, H., Shimaoka, T., Yonehara, S., Odagiri, T., Tahiro, M., Sata, T., Hasegawa, H., Seino, K-i.
  • Journal Title: Mucosal Immunol 1 Pages: 208-218
  • Peer Reviewed
• [Journal Article] Comprehensive gene expression profiling of Peyer's patch M cells, villous M-like cells, and intestinal epithelial cells (2008)
  • Author(s): Terahara, K., Yoshida, M., Igarashi, O., Nochi, T., Pontes, G. S., Hase, K., Ohno, H., Kurokawa, S., Mejima, M., Takayama, N., Yuki, Y., Lowe, A. W., Kiyono, H.
  • Journal Title: J. Immunol 180 Pages: 7840-7846
  • Peer Reviewed
• [Journal Article] Comparative genome analysis of Lactobacillus reuteri and Lactobacillus fermentum reveal a genomic island for reuterin and cobalamin production (2008)
  • Author(s): Morita, H., Toh, H., Fukuda, S., Horikawa, H., Oshima, K., Suzuki, T., Murakami, M., Hisamatsu, S., Kato, Y., Takizawa, T., Fukuoka, H., Yoshimura, T., Itoh, K., O'Sullivan, D. J., McKay, L. L., Ohno, H., Kikuchi, J., Masaoka, T., Hattori, M.
  • Journal Title: DNA Res 15 Pages: 151-161
  • Peer Reviewed
• [Journal Article] Aberrant trafficking of the high-affinity choline transporter in AP-3-deficient mice (2008)
  • Author(s): Misawa, H., Fujigaya, H., Nishimura, T., Moriwaki, Y., Okuda, T., Kawashima, K., Nakata, K., Ruggiero, A. M., Blakely, R. D., Nakatsu, F., Ohno, H.
  • Journal Title: Eur. J. Neurosci 27 Pages: 3109-3117
  • Peer Reviewed
• [Journal Article] Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease (2008)
  • Author(s): Hase, K., Takahashi, D., Ebisawa, M., Kawano, S., Itoh, K., Ohno, H.
  • Journal Title: PLoS ONE 3 Pages: e3033
  • Peer Reviewed
• [Journal Article] Splenic CD19-CD35+B220+ cells function as an inducer of the follicular dendritic cell-network formation (2007)
  • Author(s): Murakami, T., Chen, X., Hase, K., Sakamoto, A., Nishigaki, C., Ohno, H.
  • Journal Title: Blood 110 Pages: 1215-1224
  • Peer Reviewed
• [Journal Article] Construction of an open-access database that integrates cross-reference information from the transcriptome anda proteome of immune cells (2007)
  • Author(s): Hijikata, A., Kitamura, H., Kimura, Y., Yokoyama, R., Aiba, Y., Bao, Y., Fujita, S., Hase, K., Hori, S., Ishii, Y., Kanagawa, O., Kawamoto, H., Kawano, K., Koseki, H., Kibo, M., Kurita-Miki, A., Kurosaki, T., Masuda, K., Nakata, M., Oboki, K., Ohno, H., Okamoto, M., Okayama, Y., O-Wang, J., Saito, H., Saito, T., Sakuma, M., Sato, K., Seino, K., Setoguchi, R., Tamura, Y., Tanaka, M., Taniguchi, M., Taniuchi, I., Teng, A., Watanabe, T., Watarai, H., Yamasaki, S., Ohara, O.
  • Journal Title: Bioinformatics 23 Pages: 2934-2941
  • Peer Reviewed
• [Journal Article] Psg18 is specifically expressed in follicle-associated epithelium (2007)
  • Author(s): Kawano, K., Ebisawa, M., Hase, K., Fukuda, S., Hijikata, H., Kawano, S., Date, Y., Tsuneda, S., Itoh, K., Ohno, H.
  • Journal Title: Cell Struct. Funct 32 Pages: 115-126
  • Peer Reviewed
• [Presentation] Glycoprotein 2, a transcytotic receptor expressed by intestinal M cells, plays a critical role in immunosurveillance against enterobacteria (2009)
  • Author(s): Kawano, K., Hase, K., Nochi, T., Pontes, G. S., Fukuda, S., Nakato, G., Ebisawa, M., Iimura, M., Fukuoka, S., Waguri, S., Itoh, K., Kiyono, H., Ohno, H.
  • Organizer: Keystone Symposia on Molecular and Cellular Biology "Innate, Adaptive and Regulatory Immune Responses to Intestinal Microbiota"
  • Year and Date: 2009-01-16
• [Presentation] Multi-omic analysis identifies microbial metabolites to protect host from enterohaemorrhagic Escherichia coli O157:H7 lethal infection (2009)
  • Author(s): Fukuda, S., Nakanishi, Y., Toh, H., Yoshimura, K., Oshima, K., Morita, H., Tobe, T., Itoh, K., Kikuchi, J., Hattori, M., Ohno, H.
  • Organizer: Keystone Symposia on Molecular and Cellular Biology "Innate, Adaptive and Regulatory Immune Responses to Intestinal Microbiota"
  • Year and Date: 2009-01-14
• [Presentation] 通常培養状態におけるc-Jun N-terminal kinase (JNK)による翻訳制御 (2008)
  • Author(s): 伊藤誠.、北村浩、菊口千智、湯浅朋子、大野博司、小原収
  • 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
  • Year and Date: 2008-12-12
• [Presentation] バクテリア発現遺伝子情報を付与したDGGE-NMR相関解析法による腸内環境評価系の構築 (2008)
  • Author(s): 加藤完、伊達康博、福田真嗣、中西由美子、近山英輔、坪井裕理、常田聡、守屋繁春、菊地淳、大野博司
  • 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
  • Year and Date: 2008-12-11
• [Presentation] 腸内細菌の代謝変動に着目した植物性プレバイオティクス候補の探索 (2008)
  • Author(s): 中西由美子、縫島裕美、福田真嗣、加藤完、梅原三貴久、大野博司、菊地淳
  • 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
  • Year and Date: 2008-12-11
• [Presentation] リンパ濾胞上皮層における宿主-微生物相互作用の解析 (2008)
  • Author(s): 福田真嗣、大野博司
  • Organizer: Hindgut Club Japan 2008
  • Year and Date: 2008-12-06
• [Presentation] 小腸パイエル板M細胞におけるCCL9の機能解析 (2008)
  • Author(s): 山崎龍、木村俊介、長谷耕二、伊達康博、海老澤昌史、大野博司
  • Organizer: Hindgut Club Japan 2008
  • Year and Date: 2008-12-06
• [Presentation] 腸内環境を評価するためのバクテリア発現遺伝子解析法の構築 (2008)
  • Author(s): 加藤完、伊達康博、福田真嗣、中西由美子、近山英輔、坪井裕理、常田聡、守屋繁春、菊地淳、大野博司
  • Organizer: Hindgut Club Japan 2008
  • Year and Date: 2008-12-06
• [Presentation] Deficiency of epithelium-specific basolateral sorting factor AP-1B heads to spontaneous development of colitis (2008)
  • Author(s): Takahashi, D., Hase, K., Ohno, H.
  • Organizer: 第38回日本免疫学会学術集会
  • Year and Date: 2008-12-03
• [Presentation] CXCR6 is upregulated in effector CD4+ T cells infiltrating into chronically inflamed colonic tissue (2008)
  • Author(s): Mandai, Y., Takahashi, D., Hase, K., Sato, T., Ebisawa, M., Katsuno, Y., Ohno, H.
  • Organizer: 第38回日本免疫学会学術集会
  • Year and Date: 2008-12-03
• [Presentation] Comprehensive gene expression profiling of antigen-sampling M cells: Specific expression of GP2 and MLP genes by Peyer's patch M cells (2008)
  • Author(s): 吉田理人、寺原和孝、野地智法、Pontes, G. S., 長谷耕二、大野博司、幸義和、清野宏
  • Organizer: 第38回日本免疫学会学術集会
  • Year and Date: 2008-12-03
• [Presentation] Glycopotein 2 is specifically expressed on the apical membrane of Peyre's patch M cells but not Villous M cells (2008)
  • Author(s): Pontes, G. S., Toshida, M., Nochi, T., Hase, K., Ohno, H., Terahara, K., Yuki, Y., Koyono, H.
  • Organizer: 第38回日本免疫学会学術集会
  • Year and Date: 2008-12-03
• [Presentation] Comprehensive analysis of the expression of M-cell-associated proteins among mucosa-associated lymphoid tissue (2008)
  • Author(s): Date, Y., Fukuda, S., Hase, K., Tsuneda, S., Ohno, H.
  • Organizer: 第38回日本免疫学会学術集会
  • Year and Date: 2008-12-03
• [Presentation] Tunneling nanotubules formed by Peyer's patch M cells: Potential function as the antigen-transporting web (2008)
  • Author(s): Hase, K., Takatsu, H., Kimura, S., Ohno, H.
  • Organizer: 第38回日本免疫学会学術集会
  • Year and Date: 2008-12-03
• [Presentation] Spatial and temporal specific expression patterns of RANLK/RANK in developing peripheral lymphoid organs (2008)
  • Author(s): Sugiyama, M., Ohno, H., Yoshida, H.
  • Organizer: 第38回日本免疫学会学術集会
  • Year and Date: 2008-12-02
• [Presentation] Brucella abortus is taken up via intestinal M cells by interacting with cellular prion protein (2008)
  • Author(s): Nakato, G., Hase, K., Fukuda, S., Kawano, K., Ohno, H.
  • Organizer: 第38回日本免疫学会学術集会
  • Year and Date: 2008-12-02
• [Presentation] (2008) CXCR6 is upregulated in effector memory CD4+ T cells infiltrating into chronically inflamed colonic tissue (2008)
  • Author(s): Mandai, Y., Hase, K., Sato, T., Takahashi, D., Ebisawa, M., Katsuno, Y., Saito, Y., Ohno, H.
  • Organizer: Digestive Disease Week-
  • Year and Date: 2008-05-19
• [Presentation] 栄養源に伴う腸内環境変動の微生物群集構造解析法に基づく評価 (2008)
  • Author(s): 中西由美子、福田真嗣、伊達康博、加藤完、坪井裕理、常田聡、大野博司、菊地淳
  • Organizer: 日本農芸化学会2008年度大会
  • Year and Date: 2008-03-27
• [Presentation] ニュートリメタボノミクスにおける安定同位体標識技術の適用 (2007)
  • Author(s): Date, Y., Nakanishi, Y., Fukuda, S., Tsuneda, S., Ohno, H., Kikuchi, J.
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Year and Date: 2007-12-13
• [Presentation] (2007 )腸内細菌群のニュートリメタボノミクス基盤技術の構築 (2007)
  • Author(s): Nakanishi, Y., Fukuda, S., Chikayama, E,. Kimura, Y., Ohno, H., Kikuchi, J.
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Year and Date: 2007-12-13
• [Presentation] 非ストレス状態におけるJNKによる翻訳調節 (2007)
  • Author(s): Ito, M., Kitamura, H., Kikuguchi, C., Yuasa, T., Ohara, O., Ohno, H.
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Year and Date: 2007-12-13
• [Presentation] Identification of molecules expressed in FAE and M cells to be involved in mucosal immunity (2007)
  • Author(s): Kawano, K., Hase, K., Ohno, H.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Year and Date: 2007-11-21
• [Presentation] Identification of a CD11c^+CD19^+ unique cell population in the mucosa-associated lymphoid tissues: A potential role in M cell development (2007)
  • Author(s): Ebisawa, M., Hase, K., Ohno, H.
  • Organizer: 第37回日本免疫学会学術集会
  • Year and Date: 2007-11-21
• [Presentation] Epithelial-specific adaptor complex, AP-1B is essential for maintenance of immunological tolerance in the colon (2007)
  • Author(s): Takahashi, D., Hase, K., Ohno, H.
  • Organizer: 第37回日本免疫学会学術集会
  • Year and Date: 2007-11-21
• [Presentation] Bacterial adhesin is a ligand for endocytic receptor glycoprotein 2 expressed on M cells (2007)
  • Author(s): Kawano, K., Hase, K., Fukuda, S., Nakato, G., Murakami, T., Ebisawa, M., Itoh, K., Ohno, H.
  • Organizer: 第37回日本免疫学会学術集会
  • Year and Date: 2007-11-21
• [Presentation] Psg18 is specifically expressed in follicle-associated epithelium (2007)
  • Author(s): Date, Y., Ebisawa, M., Kawano, K., Fukuda, S Hase, K., Tsuneda, S., Itoh, K., Ohno, H.
  • Organizer: 第37回日本免疫学会学術集会
  • Year and Date: 2007-11-21
• [Presentation] Gene expression profiles of follicle-associated epithelium covering murine intestinal Peyer's patches in response to host-bacterial cross-talk (2007)
  • Author(s): Fukuda, S., Nakato, G., Miura, K., Date, Y., Yokosawa, K., Kawano, K., Hase, K., Tsuneda, S., Itoh, K., Ohno, H.
  • Organizer: 第37回日本免疫学会学術集会
  • Year and Date: 2007-11-21
• [Presentation] Endogenous prion protein expressed on M cells: A potential antigen uptake receptor (2007)
  • Author(s): Nakato, G., Fukuda, S., Takatsu, H., Murakami, T., Kawano, K., Hase, K., Ohno, H.
  • Organizer: 第37回日本免疫学会学術集会
  • Year and Date: 2007-11-21
• [Presentation] M-Sec: the M cell-specific Sec family molecule that regulates tunneling nanotubule (TNT) formation (2007)
  • Author(s): Hase, K., Takatsu, H., Kawano, S., Ohno, H.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Year and Date: 2007-11-20
• [Presentation] Differential gene expression profiles of follicle-associated epithelium covering murine intestinal Peyer's patches in response to host-bacterial cross-talks (2007)
  • Author(s): Fukuda, S., Nakato, G., Miura, K., Kawano, K., Hase, K., Itoh, K., Ohno, H.
  • Organizer: 13^<th> International Congress of mucosal Immunology
  • Year and Date: 2007-07-10
• [Presentation] Identification of a new endocytic receptor expressed in the apical plasma membrane of M cells (2007)
  • Author(s): Kawano, K., Hase, K., Fukuda, S., Murakami, T., Waguri, S., Itoh, K., Ohno, H.
  • Organizer: 13^<th> International Congress of mucosal Immunology
  • Year and Date: 2007-07-10
• [Presentation] Endogenous prion protein expressed on the apical plasma membrane in M cells could function as a potential antigen uptake receptor (2007)
  • Author(s): Nakato, G., Fukuda, S., Takatsu, H., Murakami, T., Kawano, K., Hase, K., Ohno, H.
  • Organizer: 13^<th> International Congress of mucosal Immunology
  • Year and Date: 2007-07-10
• [Presentation] Activation-induced cytidine deaminase deficiency causes severe gastritis with mucosal hyperplasia (2007)
  • Author(s): Hase, K., Itoh, K., Ebisawa, M., Ohshima, S., Fagarasan, S., Ohno, H.
  • Organizer: 13^<th> International Congress of mucosal Immunology
  • Year and Date: 2007-07-10
• [Presentation] Identification of CD11c^+CD19^+ cells in the mucosa-associated lymphoid tissues: A potential role in M cell development (2007)
  • Author(s): Ebisawa, M., Hase, K., Ohno, H.
  • Organizer: 13^<th> International Congress of mucosal Immunology
  • Year and Date: 2007-07-10
• [Presentation] 宿主.腸内フローラ間相互作用の解析とその評価系の構築 (2007)
  • Author(s): 福田真嗣、中藤学、中西裕美子、三浦克吉、伊藤喜久治、菊地淳、大野博司
  • Organizer: 第11回腸内細菌学会
  • Year and Date: 2007-06-12
• [Presentation] Analysis of epithelial-specific AP-1B-deficient mice (2007)
  • Author(s): Nakato, G., Yamashita, T., Yonemura, S., Sugihara, K., Nakatsu, F., Hase, K., Murakami, T., Asano, M., Ohno, H.
  • Organizer: 第40回日本発生生物学会・第59回日本細胞生物学会合同大会
  • Year and Date: 2007-05-30
• [Presentation] T CD300 antigen like family member G: A novel Ig receptor like protein exclusively expressed on capillary endothelium (2007)
  • Author(s): akatsu, H., Hase, K., Ohmae, M., Ohshima, S., Yamamoto, A., Ohno, H.
  • Organizer: 第40回日本発生生物学会・第59回日本細胞生物学会合同大会
  • Year and Date: 2007-05-30
• [Remarks] ホームページ等
  • URL: http://leib.rcai.riken.jp/riken/index.html
• [Patent(Industrial Property Rights)] IgA腎症の予測方法およびIgA腎症患者の選択方 (2009)
  • Inventor(s): 長澤康行、飯尾健一郎、猪阪善隆、福田真嗣、大野博司
  • Industrial Property Rights Holder: 国立大学法人大阪大学、独立行政法人理化学研究所
  • Industrial Property Number: 特許,特願2009-29227
  • Filing Date: 2009-02-01
• [Patent(Industrial Property Rights)] 原核生物、特に、真性細菌のcDNAの簡易な調整方法 (2008)
  • Inventor(s): 守屋繁春、加藤完、福田真嗣、大野博司、菊地淳
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Industrial Property Number: 特許,特願2008-52503
  • Filing Date: 2008-03-03