Identification and functional analyses of the target genes of transcription factor Spi-B in Peyer's patch M cells

• Project/Area Number: 25860353
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: SATO SHINTARO 東京大学, 医科学研究所, 助教 (80447333)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 粘膜免疫 / M細胞 / 抗原取り込み / パイエル板

Outline of Final Research Achievements

To reveal the functional mechanism of M cells, we tried to identify the target gene cluster of transcription factor Spi-B, which was essential to M-cell differentiation. Finally, we found three genes as an M-cell specific expression gene. Among them, we could analyze one candidate molecule (Cand1) about antigen uptake ability in vivo using the Cand1-deficient mice. As a result, the uptake of beads and Yersinia enterocolitica significantly decreased in Cand1-deficient mice when compared with a wild type mice. These results suggest that Cand1 is associated with the expression and/or activation of beta 1 integrin, which is believed as the receptor for Yersinia.

Research Products

• [Journal Article] Loss of lymph node fibroblastic reticular cells and high endothelial cells is associated with humoral immunodeficiency in mouse graft-versus-host disease. (2015)
  • Author(s): Suenaga, F., Ueha, S., Abe, J., Kosugi-Kanaya, M., Wang, Y., Yokoyama, A., Shono, Y., Shand, F. H., Morishita, Y., Kunisawa, J., Sato, S., Kiyono, H. and Matsushima, K.
  • Journal Title: J. Immunol. Volume: 194(1) Issue: 1 Pages: 398-406
  • DOI: 10.4049/jimmunol.1401022
  • Peer Reviewed / Open Access
• [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] Innate lymphoid cells regulate intestinal epithelial cell glycosylation. (2014)
  • Author(s): Goto Y, Obata T, Kunisawa J, Sato S, Ivanov II, Lamichhane A, Takeyama N, Kamioka M, Sakamoto M, Matsuki T, Uematsu S, Akira S, Domino SE, Kulig P, Becher B, Renauld JC, Sasakawa C, Umesaki Y, Benno Y, Kiyono H
  • Journal Title: Science Volume: 345 Issue: 6202 Pages: 1254009-1254009
  • DOI: 10.1126/science.1254009
  • Peer Reviewed / Open Access
• [Journal Article] Vaginal memory T cells induced by intranasal vaccination are critical for protective T cell recruitment and prevention of genital HSV-2 disease. (2014)
  • Author(s): Sato, A., Suwanto, A., Okabe, M., Sato, S., Nochi, T., Imai, T., Koyanagi, N., Kunisawa, J., Kawaguchi, Y. and Kiyono, H.
  • Journal Title: J Virol. Volume: 88(23) Issue: 23 Pages: 13699-13708
  • DOI: 10.1128/jvi.02279-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Peyer's patches and mesenteric lymph nodes cooperatively promote enteropathy in a mouse model of food allergy. (2014)
  • Author(s): Nakajima-Adachi, H., Kikuchi, A., Fujimura, Y., Shibahara, K., Makino, T., Goseki-Sone, M., Kihara-Fujioka, M., Nochi, T., Kurashima, Y., Igarashi, O., Yamamoto, M., Kunisawa, J., Toda, M., Kaminogawa, S., Sato, R., Kiyono, H., and Hachimura, S.
  • Journal Title: PLoS One. Volume: 9 Issue: 9 Pages: 108294-108294
  • DOI: 10.1371/journal.pone.0108294
  • Peer Reviewed / Open Access
• [Journal Article] Mucosal Immunosenescence in the Gastrointestinal Tract (2014)
  • Author(s): Sato, S. et al.
  • Journal Title: Gerontology Volume: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome. (2014)
  • Author(s): Takemura, N., et al.
  • Journal Title: Nature Commun. Volume: 5 Issue: 1 Pages: 3492-3492
  • DOI: 10.1038/ncomms4492
  • Peer Reviewed
• [Journal Article] Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice. (2014)
  • Author(s): Hiyama S, Iijima H, Shinzaki S, Inoue T, Shiraishi E, Kawai S, Araki M, Kato M, Hayashi Y, Nishida T, Fujii H, Mukai A, Shibata N, Sato S, Kiyono H, Gotoh K, Motooka D, Nakamura S, Iida T, Tsujii M, Takehara T.
  • Journal Title: Inflamm Bowel Dis. Volume: 5 Issue: 5 Pages: 790-9
  • DOI: 10.1097/mib.0000000000000017
  • Peer Reviewed / Open Access
• [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] The enzyme cyp26b1 mediates inhibition of mast cell activation by fibroblasts to maintain skin-barrier homeostasis. (2014)
  • Author(s): Kurashima Y, Amiya T, Fjisawa K, Shibata N, Suzuki Y, Kogure Y, Hashimoto E, Otsuka A, Kabashima K, Sato S, Sato T, Kubo M, Akira S, Miyake K, Kunisawa J, Kiyono H.
  • Journal Title: Immunity Volume: 40 Issue: 4 Pages: 530-541
  • DOI: 10.1016/j.immuni.2014.01.014
  • Peer Reviewed / Open Access
• [Journal Article] Mucosal adjuvants for vaccines to control upper respiratory infections in the elderly. (2014)
  • Author(s): Fujihashi, K., Sato S., and Kiyono, H.
  • Journal Title: Exp. Gerontol. Volume: 54 Pages: 21-26
  • DOI: 10.1016/j.exger.2014.01.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nanogel-Based PspA Intranasal Vaccine Prevents Invasive Disease and Nasal Colonization by Streptococcus pneumoniae (2013)
  • Author(s): Il Gyu Kong, Ayuko Sato, Yoshikazu Yuki, Tomonori Nochi, Haruko Takahashi, et al.
  • Journal Title: Infection and Immunity Volume: (online) Issue: 5 Pages: 1625-34
  • DOI: 10.1128/iai.00240-13
  • Peer Reviewed
• [Journal Article] An essential role for the N-terminal fragment of Toll-like receptor 9 in DNA sensing (2013)
  • Author(s): Onji M, Kanno A, Saitoh S, Fukui R, Motoi Y, Shibata T, Matsumoto F, Lamichhane A, Sato S, Kiyono H, Yamamoto K, Miyake K
  • Journal Title: Nat. Commun. Volume: 4 Issue: 1 Pages: 1949-1949
  • DOI: 10.1038/ncomms2949
  • NAID: 120005359107
  • Peer Reviewed
• [Journal Article] Critical role of dendritic cells in T cell retention in the inter-molecular region of Peyer's patches. (2013)
  • Author(s): Obata, T., et al.
  • Journal Title: J. Immunol. Volume: 191 Issue: 2 Pages: 942-948
  • DOI: 10.4049/jimmunol.1200636
  • Peer Reviewed
• [Journal Article] Transcription factor Spi-B-dependent and -independent pathways for the development of Peyer's patch M cells (2012)
  • Author(s): Sato, S., et al.
  • Journal Title: Mucosal Immunology Volume: ６ Issue: 4 Pages: 838-846
  • DOI: 10.1038/mi.2012.122
  • Peer Reviewed
• [Presentation] 抗原取り込みに特化した上皮細胞、M細胞の機能発現メカニズム (2015)
  • Author(s): 佐藤慎太郎
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-28
  • Invited
• [Presentation] Transcription factor Spi-B-dependent and -independent pathways for the development of Peyer’s patch M cells. (2013)
  • Author(s): Shintaro Sato
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan, Italy