Tohoku university school of medicine

The immune system is known to be evolved for protective mechanisms against a variety of infectious pathogens. The dysregulation of immune signals, however, causes immune disorders including allergy, autoimmune diseases, inflammatory diseases, and immunodeficiency. Over the past 10 years, we have investigated the roles of OX40/OX40 ligand, a T cell costimulatory system, in T cell memory and T cell-mediated inflammation. We have demonstrated the pathogenic mechanisms mediated by OX40 signals for autoimmunity and inflammatory bowel disease, and proposed a new therapeutic strategy for these diseases by targeting OX40 ligand. In another project, we have established NOD/Shi-scid-IL-2Rγ(γc)^null(NOG) mice, into which almost all of human cells and tissues can be transplanted because of the lack of any rejection responses in NOG mice. By using NOG mice, we are establishing a novel animal model in which the human immune system can be perfectly reconstituted, and attempting to identify cancer stem cells. The other project is regarding three mammalian Vps proteins, Hrs, STAM1 and STAM2, all of which we have originally cloned. They are important for the down-regulation of cytokine receptors and signaling molecules by a lysosomal degradation mechanism. We are investigating their effects on cytokine signaling.

1)OX40 costimulatory signals potentiate the memory commitment of effector CD8+ T cells. J. Immunol. 181: 3193-3201 2008

2)Differential requirements for OX40 signals on generation of effector and central memory CD4+ T cells. J. Immunol. 179: 5014-5023 2007

3)Therapeutic targeting of the effector T cell costimulatory molecule OX40 Nature Rev Immunol, 4: 420-431 2004

4)Distinct roles for the OX40-OX40L interaction in regulatory and non-regulatory T cells. J. Immunol., 172: 3580-3589 2004

5)Impairment of antigen-presenting cell function in mice lacking expression of OX40 ligand J. Exp. Med. 191:365-374 2000

cytokine, immunodeficiency, autoimmunity, inflammatory bowel disease, immunological memory, NOG mouse, vesicle transport, SARS