Research Theme

Our laboratory studies mechanisms of innate immunity. The innate immune system senses invading microbial pathogens and plays an essential role for induction of inflammatory responses as well as assisting adaptive immune responses. Germline-encoded pattern-recognition receptors (PRRs) expressed on innate immune cells such as macrophages and dendritic cells are responsible for recognition of pathogen-associated molecular patterns (PAMPs) which represent conserved molecular features in microbial pathogens. Through generation of knockout mice, we have demonstrated that a family of Toll-like receptors (TLR) recognizes a variety of PAMPs such as lipopolysaccharide, lipoprotein and nucleic acids derived from bacteria, viruses and protozoa to elicit innate immune responses. We have also demonstrated that a family of RIG-I-like RNA helicases (RLR) including RIG-I and MDA5 participates in TLR-independent recognition of nucleic acids derived from different types of RNA viruses in the cytoplasm. In addition, we have clarified in TLR signaling pathways that TLRs utilize different combinations of adapter molecules (MyD88, TRIF, TIRAP/Mal, TRAM) to activate different signaling pathways depending on the invading pathogen. Moreover, we have recently discovered an adapter molecule for RLR which we named IPS-1. Based on these findings, we are currently investigating following issues.

1) comprehensive analysis of gene expression in innate immune cells, using knockout mice.
2) discovery and characterization of functional molecules or cells regulating innate immune responses.
3) understanding of pathways linking between innate and adaptive immunity.
4) in vivo imaging of innate immune cells.

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