Analysis of antigen-uptake network at mucosal epithelial layer
Project/Area Number |
20249028
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Immunology
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Research Institution | The University of Tokyo |
Principal Investigator |
KIYONO Hiroshi The University of Tokyo, 医科学研究所, 教授 (10271032)
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Co-Investigator(Renkei-kenkyūsha) |
KUNISAWA Jun 東京大学, 医科学研究所, 講師 (80376615)
SATO Shintaro 東京大学, 医科学研究所, 助教 (80447333)
YUKI Yoshikazu 東京大学, 医科学研究所, 助教 (60345030)
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Project Period (FY) |
2008 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥50,830,000 (Direct Cost: ¥39,100,000、Indirect Cost: ¥11,730,000)
Fiscal Year 2010: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Fiscal Year 2009: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2008: ¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
|
Keywords | 粘膜免役 / M細胞 / 上皮細胞 / 抗原取り込み / 共生細菌 / 粘膜免疫 / UEA-1 / フコシル化 |
Research Abstract |
M (Microfold) cells and related subpopulation cells are known as specialized cells for antigen uptake. To reveal the extracellular regulating factors and the mechanisms for antigen uptake and their differentiation of M cells, we identified several M cell-specific genes, and investigated there functions on M cells. As a result, it was suggested that inducible M-like cells, which have been discovered by our group, were an intermediate cells between Peyer's patch M cells and intestinal epithelial cells. We succeeded in identifying GP2 and MLP as novel M cell-specific molecule. In the case of GP2, our collaborative efforts revealed that GP2 could capture some bacterial groups via FimH protein, and acted as a scaffold to uptake them efficiently. In addition, we established monoclonal anti-GP2 antibody, and verified that this antibody was applicable for effective vaccine antigen delivering to M cells.
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Report
(4 results)
Research Products
(77 results)
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[Journal Article] Distinct fucosylation of M cells and epithelial cells by Fut1 and Fut2, respectively, in response to intestinal environmental stress.2011
Author(s)
Terahara K, Nochi T, Yoshida M, Takahashi Y, Goto Y, Hatai H, Kurokawa S, Jang MH, Kweon MN, Domino SE, Hiroi T, Yuki Y, Tsunetsugu-Yokota Y, Kobayashi K, Kiyono H.
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Journal Title
Biochem Biophys Res Commun.
Volume: 404
Pages: 822-828
Related Report
Peer Reviewed
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[Journal Article] Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.2010
Author(s)
Nochi T, Yuki Y, Takahashi H, Sawada S, Mejima M, Kohda T, Harada N, Kong IG, Sato A, Kataoka N, Tokuhara D, Kurokawa S, Takahashi Y, Tsukada H, Kozaki S, Akiyoshi K, Kiyono H.
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Journal Title
Nat Mater.
Volume: 9
Pages: 572-578
Related Report
Peer Reviewed
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[Journal Article] In vivo molecular imaging analysis of a nasal vaccine that induces protective immunity against botulism in nonhuman primates.2010
Author(s)
Yuki Y, Nochi T, Harada N, Katakai Y, Shibata H, Mejima M, Kohda T, Tokuhara D, Kurokawa S, Takahashi Y, Ono F, Kozaki S, Terao K, Tsukada H, Kiyono H.
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Journal Title
JImmunol.
Volume: 185
Pages: 5436-5443
Related Report
Peer Reviewed
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[Journal Article] Secretory IgA-mediated protection against V.cholerae and heat-labileenterotoxin-producing enterotoxigenic Escherichia coli by rice-based vaccine.2010
Author(s)
Tokuhara D, Yuki Y, Nochi T, Kodama T, Mejima M, Kurokawa S, Takahashi Y, Nanno M, Nakanishi U, Takaiwa F, Honda T, Kiyono H.
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Journal Title
Proc Natl Acad Sci USA.
Volume: 107
Pages: 8794-8799
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Peer Reviewed
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[Journal Article] Indigenous opportunistic bacteria inhabit mammalian gut-associatedlymphoid tissues and share a mucosal antibody-mediated symbiosis.2010
Author(s)
Obata T, Goto Y, Kunisawa J, Sato S, Sakamoto M, Setoyama H, Matsuki T, Nonaka K, Shibata N, Gohda M, Kagiyama Y, Nochi T, Yuki Y, Fukuyama Y, Mukai A, Shinzaki S, Fujihashi K, Sasakawa C, Iijima H, Goto M, Umesaki Y, Benno Y, Kiyono H.
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Journal Title
Proc Natl Acad Sci USA.
Volume: 107
Pages: 7419-7424
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Peer Reviewed
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[Journal Article] IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis.2010
Author(s)
Malamut G, El Machhour R, Montcuquet N, Martin-Lanneree S, Dusanter-Fourt I, Verkarre V, Mention JJ, Rahmi G, Kiyono H, Butz EA, Brousse N, Cellier C, Cerf-Bensussan N, Meresse B.
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Journal Title
J Clin Invest.
Volume: 120
Pages: 2131-2143
Related Report
Peer Reviewed
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[Journal Article] Interleukin-1 family cytokines as mucosal vaccine adjuvants for induction of protective immunity against influenza virus.2010
Author(s)
Kayamuro H, Yoshioka Y, Abe Y, Arita S, Katayama K, Nomura T, Yoshikawa T, Kubota-Koketsu R, Ikuta K, Okamoto S, Mori Y, Kunisawa J, Kiyono H, Itoh N, Nagano K, Kamada H, Tsutsumi Y, Tsunoda S.
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Journal Title
J Vjrol.
Volume: 84
Pages: 12703-12712
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Peer Reviewed
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[Journal Article] Comprehensive gene expression analysis among peyer's patch M cells, villous M cells and intestinal epithelial cells by DNA microarray analysis.2008
Author(s)
Terahara, T., Igarashi, O., Yoshid a, M., Nochi, T., Kurokawa, S.,Takayama, N., Yuki, Y., Low, A W. and Kiyono, H.
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Journal Title
J. Immunol. 180
Pages: 7840-7846
Related Report
Peer Reviewed
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[Journal Article] Regulation of humoral and cellular gut immunity by lamina propria den dritic cells expressing Toll-like receptor 5.2008
Author(s)
Uematsu,S., Fujimoto, K., Jang, MH., Yang, BG., Jung, YJ., Nishi yama, M., Sato, S., Tsujimura, T. Yamamoto, M., Yokota, Y., Kiyno, H., Miyasaka, M., Ishii, KJ., Akira, S.
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Journal Title
Nat Immunol 9
Pages: 769-776
Related Report
Peer Reviewed
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[Journal Article] Cutting edge: Langerin+ dendritic cells in the mesenteric lymph node set the stage for skin and gut immune system cross-talk2008
Author(s)
Chang, SY., Cha, HR., Igarashi, O., Rennert, PD., Kissenpfennig, A., Malissen, B., Nanrto, M., Kiy. ono, H., and Kweon, MN.
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Journal Title
J. Imrnuriol. 180
Pages: 4361-4365
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Peer Reviewed
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[Journal Article] Sphingosine 1-phosphate regulates the egress of IgA plasmablasts from Peyer's patches for intestinal IgA responses.2008
Author(s)
Gohda, M., Kunisawa, J., Miura, F., Kagiyama, Y., Kurashima, Y. , Higuchi, M., Ishikawa, I., Ogahara, I. and Kiyono, H.
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Journal Title
J. Immunol. 180
Pages: 5335-5343
Related Report
Peer Reviewed
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[Journal Article] Colonic patches direct the cross-talk between systemic compartments and large intestine independently of innate immunity.2008
Author(s)
Sun-Young Chang, Hye-Ran Cha, Uematsu, S., Akira, S., Igaras hi, O., Kiyono, H.,and Mi-Na Kweon
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Journal Title
J. Immunol 180
Pages: 1609-1618
Related Report
Peer Reviewed
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[Journal Article] Sphingosine 1-phosphate-dependent trafficking of peritoneal B cells requires functional NFkB-inducing kinase in stromal cells.2008
Author(s)
Kunisawa, J., Gohda, M., Kurashima, Y., Ishikawa, I., Higuchi, M . and Kiyono, H.
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Journal Title
Blood. 111
Pages: 4646-4652
Related Report
Peer Reviewed
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[Journal Article] Peyer's patches are required for intestinal IgA responses to Salmonella.2008
Author(s)
Hashizume, T., Togawa, A., Nochi, T., Igarashi, O., Kweon, M. N. , Kiyono, H. and Yamamoto, M.
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Journal Title
Infect Immun. 76
Pages: 927-934
Related Report
Peer Reviewed
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[Journal Article] Nasal Vaccination with the 40-Kilodalton outer membrane protein of Porphyromonas gingivalis and a nontoxic chimeric enterotoxin adjuvant induces lomg-term protective immunity with reduced levels of immunoglobulin E antibodies.2008
Author(s)
Momoi, F., Hashizume, T., Kurita-Ochiai, T., Yuki, Y., Kiyono, H ., and Yamamoto, M.
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Journal Title
Infect Immun. 76
Pages: 7840-7846
Related Report
Peer Reviewed
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