免疫シグナル研究グループ

免疫応答と恒常性制御の中心的役割を担うT細胞の分化・活性化・機能発現およびその制御のメカニズムを研究しています。免疫シナプス・シグナル伝達・細胞分化などの制御機構を解明し、これらに関与する分子を標的とするT細胞を中心とする免疫制御の確立を目指します。とくに、T細胞の機能・活性化制御の異常に基づく自己免疫疾患の発症機構を解明することによって、自己免疫疾患の制御を目指します。

研究分野

生物学 & 生化学 / 分子生物 & 遺伝学 / 免疫学 / 臨床医学

研究テーマ

• T細胞の活性化と寛容のシグナル制御
• 免疫シナプスと活性化の時空間的制御
• 自然免疫と獲得免疫のシグナル制御

主要論文

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)