In the Division of Molecular Immunology, we are investigating molecular machinery underlying immune responses against pathogen infections, including viruses and fungi. We focus on the sensor molecules in innate immune system, and aim to understand regulation and dysregulation of immune responses.
Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) triggers innate immune responses, which lead to swift eradication of the infected pathogens. In the case of viral infection, RIG-I-like receptor (RLR) family members, RIG-I, MDA5 and LGP2, are responsible for detection of viral non-self RNA as PAMPs, and activate expression of anti-viral cytokine, including type I interferon. In this project, we focus on function of RLRs in anti-viral immune responses.
1. Among three RLRs, RIG-I and MDA5 detect 5'-triphsphate containing short double-stranded RNA (dsRNA) and long dsRNA, respectively. We try to understand molecular mechanism(s) underlying recognition of the substrates by RLRs using molecular biological, cell biological and biochemical approaches.
2. RLRs is known to detect viral non-self RNA, however it remains unclear whether RLRs interact with "self" RNAs. We are interested in possible interaction between RLRs and endogenous RNAs and concomitant biological significance.
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- Yoneyama, M. et al., J. Immunol., 175 2851-2858, 2005.
- Yoneyama, M. et al., Nat. Immunol., 5, 730-737, 2004.
The immune system is composed of a network of cells, tissues and organs that works to protect from pathogens. Cytokines facilitate the system by transducing signaling among these cells. In this project, we aim to reveal host defense mechanisms by investigating the roles of cytokines in innate and acquired immune responses.
1. The roles of C-type lectins in innate and acquired immunity.
The C-type lectins are a group of proteins that have a Ca2+-dependent- or -independent -carbohydrate-recognition domain in their extracellular carboxyterminal domains. Some C-type lectin family members recognize the carbohydrate structures of microbes as pathogen-associated molecular patterns which lead to cytokine production and reactive oxygen production. In this project, using gene-deficient mice, we investigate functions of C-type lectins expressed in DCs or macrophages.
2. Mechanisms of cytokine-induced protective immunity and diseases.
Cytokines play a central role in T cell differentiation, a series of events initiated by the sensing, processing and displaying of invading pathogens by antigen-presenting cells. However, an excess of cytokine production causes inflammatory diseases including autoimmune diseases. We aim to find new therapeutic targets for inflammatory diseases and infectious diseases by investigating the roles of cytokines in pathogenesis.