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 - Institute for Frontier Medical Sciences
Experimental Pathology
Field of Biological Function
Our Department is studying how the immune system controls physiological and pathological immune responses. Our main interest is in understanding the mechanism of immunologic unresponsiveness to self-constituents (i.e., immunologic self-tolerance) to determine the cause and mechanism of autoimmune disease, to develop the ways to provoke effective tumor immunity, and to establish stable immunologic tolerance to organ-transplants.

  Shimon Sakaguchi, M.D., Ph.D
Research and Education
The aim of this department in education and research is to provide a good opportunity for students to learn immunology and help them establish themselves as researchers in immunology and medicine. Our research is currently focused on understanding the mechanisms of immunologic self-tolerance (i.e. immunological unresponsiveness of the normal immune system to normal self-constituents). We specifically study: (i) the cellular and molecular basis of immunologic self-tolerance and the etio-pathology of autoimmune disease; (ii) the strategy for eliciting effective immune responses to autologous tumor cells, or inducing immunologic tolerance to organ transplants, by manipulating the mechanism of immunologic self-tolerance; and (iii) the cause and pathogenetic mechanism of rheumatoid arthritis by analyzing an animal model newly established in our laboratory.

Experimental Pathology
Institute for Frontier Medical Sciences
Professor Shimon Sakaguchi
TEL +81-75-751-3851
FAX +81-75-751-3820
Defects in immune regulation mediated by regulatory T cells cause autoimmune gastritis accompanying anti-parietal cell autoantibody, autoimmune thyroiditis, and insulitis of Langerhans’ islets of the pancreas as observed in human type 1 diabetes.
Regulatory T cells control hazardous autoimmune T cells, thereby preventing autoimmune disease.
Recent Publications
1. Sakaguchi, S.: Naturally arising CD4+ regulatory T cells for immunologic self-tolelance and negative control of immune responses. Ann. Rev. Immunol. 22:531-562, 2004.
2. Sakaguchi1, N., Takahashi1, T., Hata, H., Nomura, T., Tagami, T., Yamazaki, S., Sakihama, T., Matsutani, T., Negishi, I., Nakatsuru1, S., and Sakaguchi, S.: Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature. 426:454-60, 2003.
3. Hori, S., Nomura, T., and Sakaguchi, S.: Control of regulatory T cell development by the transcription factor Foxp3. Science. 299: 1057-1061, 2003.
4. Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y., and Sakaguchi, S.: Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance. Nature Immunol. 3: 135-142, 2002.