| MPA1 | |
| Project ID |  MPA1 [Protein] |
| Project Theme | Structural analysis of molecules related to the innate immune system |
| Project Theme (short) | Innate immunity molecules |
| Principal Investigator | Ken Ishii |
| Affiliation | Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation |
| Backgrounds | - Nucleic acids (DNA and RNA) are found to induce the innate immunity - We will elucidate detailed molecular mechanism by which sensor molecules, Toll-like receptors, recognize DNAs - Understanding of the mechanism of innate immunity could lead to DNA vaccination and therapeutic developments for autoimmune diseases |
| Highlights | - Molecular mechanisms of TLR9 and TLR7 mediated innate immunity induced by nucleic acids have been elucidated - Action mechanisms of DNA vaccines and influenza vaccines have been revealed - Structural analyses of TLRs are in progress - We found that alum adjuvant causes cell death and the subsequent release of host cell DNA, which acts as a potent endogenous immunostimulatory signal |
| Outline | Rapid advances in our understanding of innate immune systems, which provide immediate defense against infection prior to adaptive immune system, have revealed that nucleic acids (DNA and RNA) induce the innate immunity. Nucleic acids are first recognized by sensor molecules, Toll-like receptors (TLRs). Among ten TLRs identified in humans, several TLRs including TLR9 recognize nucleic acids and mediate signal transduction inside cells, resulting in the formation of interferons and cytokines. Recently, CpG oligodeoxynucleotides DNAs with specific 6-base sequences have attracted considerable attention, since they are caught by TLR9 and are found to exhibit anticancer, antiallergy and infection resistance effects in mice. We would like to elucidate detailed molecular mechanism by which TLR9 recognizes DNAs. Since we have already crystallized a TLR9-DNA complex, its structural determination will be pursued. |
| Review | Ann. N. Y. Acad. Sci. Immunol. Rev. Int. Immunol. Biochem. Biophys. Res. Commun. Cell J. Allergy Clin. Immunol. J. Cell Biol. Expert Rev Vaccines |
| CSML File | MPA1.csml |