Immune Signal Unit (Hiroki Ishikawa)

Project overview

Immune system comprises a variety of immune cell populations which are distinguished by their functions and phenotypes. The diversity of immune cells and usage of a proper set of the subsets are necessary to combat a wide range of pathogens while maintaining self-tolerance. Our lab is interested in the molecular mechanisms contribute to generate diversity of immune cells. Using genetically modified mouse models, we have studied differentiation mechanisms of immune cells and identified critical functions of AP-1 transcription factors in expansion of functional diversity of autoimmune T helper cells. This provides new insights into how heterogeneous immune cells are generated in a context dependent manner. Furthermore, the data would contribute to develop new therapeutic strategies to control a specific immune response by targeting a small subset of immune cells.

References

  • S. Koizumi, D. Sasaki, T. Hsieh, N. Taira, N. Arakaki, S. Yamasaki, K. Wang, S. Sarkar,  H. Shirahata, M. Miyagi, H. Ishikawa "JunB regulates homeostasis and suppressive functions of effector regulatory T cells"  Nat. commun. 9, 5344, 2018
  • Z. Hasan, S. Koizumi, D. Sasaki, H. Yamada, N. Arakaki, Y. Fujihara,　S. Okitsu, H. Shirahata, and H. Ishikawa “JunB is essential for IL-23-dependent pathogenicity of Th17 cells” Nat. commun.8:15628, 2017
  • H. Chen, H. Sun, F. You, W. Sun, X. Zhou, L. Chen, J. Yang, Y. Wang, H. Tang, Y. Guan, W. Xia, J. Gu, H. Ishikawa, D. Gutman, G. Barber, Z. Qin, Z. Jiang “Activation of STAT6 by STING is critical for antiviral innate immunity” Cell 147, 436-446, 2011
  • H. Ishikawa and G. Barber “The STING pathway and regulation of innate immune signaling in response to DNA pathogens” Cell Mol. Life Sci. 68, 1157-1165, 2011
  • H. Ishikawa, Z. Ma, and G. Barber “STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity” Nature 461, 788-792, 2009
  • H. Ishikawa and G. Barber “STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling.” Nature 455, 674-8, 2008