Laboratory for Cell Signaling

The general goal of this laboratory is to elucidate the mechanism of activation, differentiation and functional and its regulation of T cells which play central roles in the regulation of immune responses and homeostasis. These include the regulation of immunological synapse, TCR signal transduction, co-stimulation regulation and signaling in T cell development. Particularly, the mechanism to induce autoimmune diseases caused by aberrant regulation of T cell function and activation will be analyzed to aim to overcome the diseases.

Research Fields

Biology & Biochemistry / Molecular Biology & Genetics / Immunology / Clinical Medicine

Research Subjects

• Regulation of activation and tolerance of T cells
• Spatial and temporal regulation of immunological synapse and cell activation
• Signal Interface of innate and acquired immunity

Publications

1. Yokosuka, T., Takamatsu, M., Kobayashi-Imanishi, W., Hashimoto-Tane, A., Azuma, M. and Saito, T.:
   "Programmed cell death-1 forms negative costimulatory microclusters that directly inhibit T cell receptor signals by recruitment of phosphatase SHP2."
   J. Exp. Med. 209:1201-1217 (2012).
2. Hashimoto-Tane A., Yokosuka T., Sakata-Sogawa K., Sakuma M., Ishihara C., Tokunaga M., Saito T.:
   "Dynein-driven transport of T cell receptor microclusters regulates immune synapse formation and T cell activation."
   Immunity. 34:919-931(2011)
3. Yokosuka T, Kobayashi W, Takamatsu M, Sakata-Sogawa K, Zeng H, Hashimoto-Tane A, Yagita H, Tokunaga M, Saito T.:
   "Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation"
   Immunity. 33:326-339(2010)
4. Takeuchi A, Itoh Y, Takumi A, Ishihara C, Arase N, Yokosuka T, Koseki H, Yamasaki S, Takai Y, Miyoshi J, Ogasawara K,, Saito T.:
   "CRTAM confers late-stage activation of CD8+ T cells to regulate retention within lymph node."
   J. Immunol. 183:4220-4228(2009)
5. Yokosuka, T., Kobayashi, W., Sakata-Sogawa, K., Hashimoto-Tane, A., Dustin, M.L., Tokunaga, M., Saito, T.:
   "Spatiotemporal regulation of T cell costimulation by TCR-CD28 microclusters through protein kinase C θ translocation."
   Immunity. 29: 589-601(2008)
6. Yamasaki, S., Ishikawa, E., Sakuma, M., Ogata, K., Saito, T.:
   "Mincle is an ITAM-coupled activating receptor that senses damaged cells."
   Nat. Immunol. 9:1179-1188(2008)
7. Hara, H.,Ishihara C., Takeuchi, A., Imanishi, T., Xue, L., Morris, SW., Inui, M., Takai, T., Shibuya, A., Saijo, S., Iwakura, Y., Ohno, N., Koseki, H., Yoshida, H., Penninger, JM., Saito, T.:
   "The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors."
   Nat. Immunol. 8:619-629(2007)
8. Suzuki, N., Suzuki, S., Millar, D. G., Unno, M., Hara, H., Calzascia, T., Yamasaki, S., Yokosuka, T., Chen, N-J., Elford, A. R., Suzuki, J-I., Takeuchi, A., Mirtsos, C., Bouchard, D., Ohashi, P. S., Yeh, W-C., Saito, T.:
   "A critical role for the innate immune signaling molecule IRAK-4 in T cell activation."
   Science 311:1927-1932(2006)
9. Yamasaki, S., Ishikawa, E., Sakuma, M., Ogata, K., Sakata-Sogawa, K., Hiroshima, M., Wiest, D.L., Tokunaga, M., Saito, T.:
   "Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development."
   Nat. Immunol., 7:67-75 (2006)
10. Yokosuka, T., Sakata-Sogawa, K., Kobayashi, W., Hiroshima, M., Hashimoto-Tane, A., Tokunaga, M., Dustin, M.L., Saito, T.:
    "Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of ZAP 70 and SLP-76."
    Nat. Immunol., 6:1253-1262 (2005)