Laboratory for Epithelial Immunobiology
Research Areas
| 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. |  Team Leader Hiroshi OHNO (M.D.,Ph.D.)  |
Research Subjects
| (1) | Molecular mechanisms underlying the differentiation and function of FAE and M cells |
| (2) | Analysis of host-indigenous bacterial cross-talk via transcriptomic, proteomic and metabolomic approach |
List of Selected Publications
| (1) | Murakami, T., Chen, X., Hase, K., Sakamoto, A., Nishigaki, C., and Ohno, H.: "Splenic CD19-CD35+B220+ cells function as an inducer of the follicular dendritic cell-network formation." Blood, 110 (4), 1215-1224 (2007) |
| (2) | Hase, K., Murakami, T., Takatsu, H., Shimaoka, T., Iimura, M., Hamura, K., Kawano, K., Ohshima, S., Chihara, R., Itoh, K, Yonehara, S., and 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) |
| (3) | Fujimoto, M., Takatsu, H., and Ohno, H.: "CMRF-35-like molecule-5 constitutes novel paired receptors, with CMRF-35-like molecule-1, to transduce activation signal upon association with FcRγ." Int. Immunol. 18 (10), 1499-1508 (2006) |
| (4) | Mitsunari, T., Nakatsu, F., Shioda, N., Love, P.E., Grinberg, A., Bonifacino, J.S., and Ohno, H.: "Clathrin adaptor AP-2 is essential for early embryonal development." Mol. Cell. Biol. 25 (21), 9318-9323 (2005) |
| (5) | Hase, K., Ohshima, S., Kawano, K., Hashimoto, N., Matsumoto, K., Saito, H., and Ohno, H.: "Distinct gene expession profiles characterize cellular phenotypes of follicle-associated epithelium and M cells." DNA Res. 12 (2), 127-137 (2005) |
| (6) | 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., and 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) |
| (7) | Sugimoto, H., Sugahara, M., Folsch, H., Koide, Y., Nakatsu, F., Tanaka, N., Nishimura, T., Furukawa, M., Mullins, C., Nakamura, N., Mellman, I., and Ohno, H.: "Differential recognition of tyrosine-based basolateral signals by the AP-1B subunit μ1B in polarized epithelial cells." Mol. Biol. Cell 13(7), 2374-2382 (2002) |
| (8) | Folsch, H., Ohno, H., Bonifacino, J. S., and Mellman, I.: "A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells." Cell 99(2), 189-198 (1999) |
| (9) | Shiratori, T., Miyatake, S., Ohno, H., Nakaseko, C., Bonifacino, J.S., and Saito, T.: "Tyrosine phosphorylation controls internalization of CTLA4 by regulating its interaction with clathrin-associated adaptor complex AP-2." Immunity 6(5), 583-589 (1997) |
| (10) | 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) |