Department of Immunology
Professor
Tadatsugu Taniguchi, Ph.D.
Lecturer
Akinori Takaoka, M.D., Ph.D.
Assistant Professor
Kenya Honda, M.D., Ph.D. Yusuke Ohba, M.D., Ph.D.

Teaching Activities
Our teaching responsibility is to give lectures on Immunobiology, Immunochemistry and Molecular Immunology to the undergraduate students of the Faculty. It is also our responsibility to give laboratory courses on basic immunology to the students. In addition to lectures and laboratory courses by our own staff members, special lectures are given by the experts from outsides of the Faculty. We also offer a special training course (free quarter) of basic and advanced biological and immunological techniques to medical students.
Education of the graduate students is based on a weekly conference where the students present the progress of their own research projects and discuss on their future directions. Lectures on leading research activities are given by active researchers from overseas whenever they visit our department. The students may learn a profound interest of the field through the lectures.

Research Activities
Our research field covers the cellular and molecular immunology in general. Once an immune response is initiated by an antigenic stimulus, the magnitude of the response is controlled by the complex mechanisms. We have been extensively analyzing the mechanisms that function in the regulation of gene expression and signal transduction in host defense systems. Especially, we have focused on function of interleukin-2 (IL-2) and IL-2 receptors (IL-2R) to clarify the mechanisms of cell growth, differentiation and cell death functioning in lymphoid cells. We have discovered several nonreceptor type tyrosine kinases which associate with IL-2R, and have been extensively analyzing the functional role of those molecules. In addition, work is in progress to assess the role of the IL-2R subcomponent in the suppression of the immune system, by taking a novel in vivo approach.
We also focus on the molecular mechanisms of host defense against viral and bacterial infection. Among these mechanism, interferon (IFN) system is the most powerful and important system which controls the infection. During the course of the study, we have identified interferon regulatory factor-1 and -2 (IRF-1 and -2) which function as a transcriptional activator and repressor, respectively. A number of IFN-inducible genes have been shown to be involved in regulating cell proliferation and are potential critical target genes of the IRFs. To further evaluate the diverse biological effect of IRFs in vivo, we established the IRF-1 and -2 gene targeted mouse. This study also led us to discover new links between the IFN-IRF system and the tumor suppressor p53. We have also been studying IRF-3 and IRF-7, another IRF-family members, in the context of the regulation of the IFN production and action, by generating mice lacking these transcription factors. Using these gene manipulated mice, we are in the process of gaining new insights into the immune defense mechanisms. More recently, we have also been working on the regulation and function of antigen presenting cells, particularly the dendriticc cell (DC) subsets. It is becoming clear that several of the IRF family of transcription factors play critical to regulate these DC subsets.
A new staff member, Dr. Yusuke Ohba, recently joined our laboratory, and he is an expert in the field of molecular imaging techniques. Thus, we hope to gain further insights into how signaling molecules and transcription factors described above move within the immune cells, so as to effectively function in during immune responses.

References
  1. Taniguchi, T., Ogasawara, K., Takaoka, A. and Tanaka, N.; IRF Family of Transcription Factors as The Regulators of Host Defense. (2001) Annu. Rev. Immunol., 19, 623-655.
  2. Taniguchi, T. and Takaoka, A.; A weak signal for strong responses: interferon-a/b revisited. (2001). Nature Reviews Mol. Cell Biol., 2, 378-386.
  3. Nakaya, T., Sato, M., Hata, N., Asagiri, M., Suemori, H., Noguchi, S., Tanaka, N. and Taniguchi, T.; Gene induction pathways mediated by distinct IRFs during viral infection. (2001). Biochem. Biophys. Res. Commun., 283, 1150-1156.
  4. Hata, N., Sato, M., Takaoka, A., Asagiri, M., Tanaka, N. and Taniguchi T.; Constitutive IFN-a/b signal for efficient IFN-a/b gene induction by virus. (2001). Biochem. Biophys. Res. Commun., 285, 518-525.
  5. Mitani, Y., Takaoka, A., Kim, S.H., Kato, Y., Yokochi, T., Tanaka, N. and Taniguchi, T.; Cross talk of the interferon-a/b signalling complex with gp130 for effective interleukin-6 signalling. (2001). Genes Cells, 6, 631-640.
  6. Sato, K., Hida, S., Takayanagi, H., Yokochi, T., Kayagaki, N., Takeda, K., Yagita, H., Okumura, K., Tanaka, N., Taniguchi, T. and Ogasawara, K.; Antiviral response by natural killer cells through TRAIL gene induction by IFN-a/b. (2001). Eur. J. Immunol., 31, 3138-3146.
  7. Ogasawara, K., Hida, S., Weng, Y., Saiura, A., Sato, K., Takayanagi, H., Sakaguchi, S., Yokochi, T., Kodama, T., Naitoh, M., De Martino, J.A. and Taniguchi, T.; Requirement of the IFN-a/b-induced CXCR3 chemokine signalling for CD8+ T cell activation. (2002). Genes Cells., 7, 309-320.
  8. Taniguchi, T. and Takaoka, A.; The interferon-a/b system in antiviral responses: a multimodal machinery of gene regulation by the IRF family of transcription factors. (2002). Curr. Opin. Immunol., 14, 111-116.
  9. Takayanagi, H., Kim, S., Matsuo, K., Suzuki, H., Suzuki, T., Sato, K., Yokochi, T., Oda, H., Nakamura, K., Ida, N., Wagner, EF. and Taniguchi, T..; RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-b. (2002). Nature, 416, 744-9.
  10. Takayanagi, H., Kim, S., and Taniguchi, T.; Signaling crosstalk between RANKLand interferons in osteoclast differentiation (2002) Arthritis Res,4 (suppl 3):S227-S232.
  11. Takayanagi, H., Kim, S., Koga, T., and Taniguchi, T.:Induction and activation of the transcription factor NFATc1(NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts (2002). Developmental Cell,3, 889-901.
  12. Takaoka, A., and Taniguchi, T.; New aspects of IFN-α/β signaling in immunity, oncogenesis and bone metabolism (2003). Cancer Science, 94, 405-411.
  13. Sakaguchi, S., Negishi, H., Asagiri, M., Nakajima, C., Mizutani,, T., Takaoka, A., Honda, K., and Taniguchi, T.; Essential role of IRF-3 in lipopolysaccharide-induced interferon-β gene expression and endotoxin shock. (2003) Biochem Biophys Res Commun 306, 806-866.
  14. Takaoka, A., Hayakawa, K., Yanai, H., Stoiber, D., Negishi, H., Kikuchi, H., Shibue, T., Honda, K., and Taniguchi, T.; Integration of IFN-a/b signalling to p53 responses in tumor suppression and antiviral defense. (2003) Nature, 424, 516-523.
  15. Kim, S., Koga T., Isobe, M., Kern, B. E., Yokochi T., Karsenty, G., Taniguchi T., and Takayanagi,H.; Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation. (2003) Genes. Dev., 17, 1979-1991.
  16. Shibue, T., Takeda, K., Oda, E., Tanaka, H., Murasawa, H., Takaoka, A., Morishita, Y., Akira, S., Taniguchi, T., and Nobuyuki Tanaka, N.; Integral role of Noxa in p53-mediated apoptotic response. (2003) Genes. Dev. , 17, 2233-2238.
  17. Honda, K., Sakaguchi, S., Nakajima, C., Watanabe, A., Yanai, H., Matsumoto, M., Ohteki, T., Kaisho, T., Takaoka, A., Akira, S., Seya, T., and Taniguchi, T.; Selective contribution of IFN-a/bsignaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection. (2003) Proc. Natl. Acad. Sci. USA , 100, 10872-10877.
  18. Urushibara, M., Takayanagi, H., Koga, T., Kim, S., Isobe, MM., Morishita, Y., Nakagawa, T., Loeffler, M., Kodama, T., Kurosawa, H., and Taniguchi, T.; The antirheumatic drug leflunomide inhibits osteoclastogenesis by interfering with receptor activator of NF-kB ligand-stimmulated induction of nuclear factor of activated T cells c1. (2003) Arthritis & Rheumatism, 50, 794-804.
  19. Honda, K., Mizutani, T. and Taniguchi, T.; Negative regulation of IFN-a/b signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells. (2004) Proc. Natl. Acad. Sci. USA, 101, 2416-2421.
Annual Report of the Graduate School of Medicine and The Faculty of Medicine The University of Tokyo Reports for the Period April 2002 - March 2004