Laboratory for Epithelial Immunobiology
Team Leader
Hiroshi OHNO (M.D.,Ph.D.)
The mucosal epithelium that lines the inner surfaces of the body, especially within the intestine, is exposed to various macromolecules and microorganisms whose efficient uptake is crucial to maintaining normal immune regulation. Epithelial cells that cover the gut-associated lymphoid tissue (GALT), such as Peyer's patches (PP) and isolated lymphoid follicles, are both histologically and biochemically distinct from normal absorptive epithelial cells of the villi and are termed follicle-associated epithelium (FAE). FAE contains a specialized subset of epithelial cells, M cells, that play an important role in immune surveillance by delivering ingested macromolecules and microorganisms to the underlying lymphoid cells via transcytosis. Despite their significance, studies of M cells remain in their infancy, mainly because the low frequency of M cells and the lack of specific surface markers make it difficult to purify the M cells required for molecular/biochemical analyses. Accordingly, one of the primary aims of our laboratory is to understand the mechanisms that underlie the differentiation and function of FAE and M cells. Our research team is also investigating the recognition of commensal microbiota by intestinal epithelium and its influence on the mucosal and systemic immune system.
- Molecular mechanisms underlying the differentiation and function of FAE and M cells
- Analysis of host-indigenous bacterial cross-talk via transcriptomic, proteomic and metabolomic approach
- January 27, 2011
- Discovery of "probiotic transporters" unlocks secrets of infection-preventive bifidobacteria
- November 23, 2009
- Identification of "M-Sec", a formation factor of cell-ligating membrane nano-tubes
- November 12, 2009
- Key mucosal immune response mechanism identified
- October 26, 2009
- Unlocking the secrets of early immune response
- May 24, 2007
- Discovery of dendritic cell precursors which are important to the ripening of B-cells generating antigens
- January 29, 2010
- Helping cells reach out
An unexpected result leads to new insights about a poorly understood mode of communication between cells
- Fukuda, S., Toh, H., Hase, K., Oshima, K., Nakanishi, Y., Yoshimura, K., Tobe, T., Clarke, J. M., Topping, D. L., Suzuki, T., Taylor, T. D., Itoh, K., Kikuchi, J., Morita, H., Hattori, M., Ohno, H.
"Bifidobacteria can protect from enteropathogenic infection through production of acetate"
Nature, 469 (7331), 543-547(2011) - Hase, K., Kawano, K., Nochi, T., Pontes, G. S., Fukuda, S., Ebisawa, M., Kadokura, K., Tobe, T., Fujimura, Y., Kawano, S., Nakato, G., Kimura, S., Murakami, T., Iimura, M., Hamura, K., Fukuoka, S. I., Lowe, A. W., Waguri, S., Itoh, K, Kiyono, H., Ohno, H.
"Uptake via Glycoprotein 2 of FimH+ bacteria by M cells initiates mucosal immune response"
Nature 462 (7270), 226-230 (2009) - Hase, K., Kimura, S., Takatsu, H., Ohmae, M., Kawano, S., Kitamura, H., Ito, M., Watarai, H., Hazelet, C. C., Yeaman, C., Ohno, H.
"M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex"
Nature Cell Biol. 11(12), 1427-1432 (2009) - Murakami, T., Chen, X., Hase, K., Sakamoto, A., Nishigaki, C., Ohno, H.
"Splenic CD19-CD35+B220+ cells function as an inducer of the follicular dendritic cell-network formation"
Blood, 110 (4), 1215-1224 (2007) - Hase, K., Murakami, T., Takatsu, H., Shimaoka, T., Iimura, M., Hamura, K., Kawano, K., Ohshima, S., Chihara, R., Itoh, K, Yonehara, S., Ohno, H.
"The membrane-bound chemokine CXCL16 expressed on follicle-associated epithelium and M cells mediates lympho-epithelial interaction in GALT"
J. Immunol., 176 (1), 43-51 (2006) - Nakatsu, F., Okada, M., Mori, F., Kumazawa, N., Iwasa, H., Zhu, G., Kasagi, Y,, Kamiya, H., Harada, A., Nishimura, K., Takeuchi, A., Miyazaki, T., Watanabe, M., Yuasa, S., Manabe, T., Wakabayashi, K., Kaneko, S., Saito, T., Ohno, H.
"Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor"
J. Cell Biol. 167(2), 293-302 (2004) - Hase, K., Ohshima, S., Kawano, K., Hashimoto, N., Matsumoto, K., Saito, H., Ohno, H.
"Distinct gene expession profiles characterize cellular phenotypes of follicle-associated epithelium and M cells"
DNA Res. 12 (2), 127-137 (2005) - Nakatsu, F., Okada, M., Mori, F., Kumazawa, N., Iwasa, H., Zhu, G., Kasagi, Y,, Kamiya, H., Harada, A., Nishimura, K., Takeuchi, A., Miyazaki, T., Watanabe, M., Yuasa, S., Manabe, T., Wakabayashi, K., Kaneko, S., Saito, T., Ohno, H.
"Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor"
J. Cell Biol. 167(2), 293-302 (2004) - Folsch, H., Ohno, H., Bonifacino, J. S., Mellman, I.
"A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells"
Cell 99(2), 189-198 (1999) - Ohno, H., Stewart, J., Fournier, M-C., Bosshart, H., Rhee, I., Miyatake, S., Saito, T., Gallusser, A., Kirchhausen, T., Bonifacino, J.S.
"Interaction of tyrosine-based sorting signals with the medium chains of clathrin-associated protein complexes"
Science 269(5232), 1872-1875 (1995)
Principal Investigator
- Hiroshi OHNO
- Team Leader
Members
- Shinji FUKUDA
- Daisuke TAKAHASHI
- Takashi KANAYA
- Gaku NAKATO
- Toshi JINNOHARA
- Tamotsu KATO
- Yoshiko USAMI
- Kazunori KADOKURA
- Yuhki OBATA
- Akemi FUJIWARA
- Hideaki SHIMA
- Yuki KITAHARA
- Keiko KATO
- Takao SATOU
- Ai TAKAHASHI
- Shunji YAMADA
- Tsutomu SHIMIZU
- Kanako MORO
- Yuzo YAMAMOTO
- Misaho HANAZATO
- Masumi OHMAE
- Chikako UETAKE
- Satoshi OONAWA
- Yumiko FUJIMURA
- Ayako SAKAMOTO
- Tomoko HONDO
- Visiting Scientist
- Machiko SUGIYAMA
- Visiting Scientist
- Noriaki ARAKAWA
- Visiting Scientist
- Masashi EBISAWA
- Visiting Scientist
- Masaru YOSHIDA
- Visiting Scientist
- Shunsuke KIMURA
- Visiting Scientist
- Akira SHIGEHISA
- Visiting Scientist
- Yuki KAWAMURA
- Visiting Scientist
- Taeko DOHI
- Visiting Scientist
- Hirosuke SUGAHARA
- Visiting Scientist
- Minh-Hue NGUYEN
- Visiting Scientist
- Yumi CHIBA
- Sayuri SAKAKIBARA
- Kumiko NAKAI