Our laboratory was established in April 2018 in Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University. We are focusing on innate immunity to elucidate the mechanism of chronic inflammation and to develop therapeutics for immune diseases.
Toll-like receptors（TLRs） are critical for the recognition of microbial products and the induction of innate immune responses against pathogens. We previously demonstrated that a secreted molecule MD-2 is associated with the extracellular portion of TLR4 and is essential for the recognition of bacterial lipopolysaccharide (LPS)（Nagai Y et al. Nat Immunol 2002）. We also showed that TLR family proteins regulate innate immune responses and hematopoietic development（Nagai Y et al. Blood 2002; Nagai Y et al. J Immunol 2005; Nagai Y et al. Int Immunol 2012; Yanagibashi T et al. Immunol Lett 2015; Nagai Y et al. Immunity 2006）. Furthermore, we identified novel roles of TLR family proteins in the pathogenesis of chronic inflammatory diseases, such as autoimmune diseases and metabolic syndrome（Sasaki S et al. Mol Immunol 2012; Watanabe Y et al. Diabetes 2012）. Therefore, TLRs are attractive candidate for linking innate immune responses to chronic sterile inflammation.
Based on these findings, we are focusing on natural products and compounds that can regulate innate immune responses, and are screening a lead compound that activates or inhibits TLR activation. We recently found a novel TLR4 activator or inhibitor, a NLRP3 inflammasome inhibitor, and a TLR7 inhibitor（Okamoto N, et al. J Biol Chem 2017; Honda H et al. J Leukoc Biol 2012, Honda H et al. J Leukoc Biol 2014, Watanabe Y et al. Sci Rep 2016）. We are now analyzing the mechanism of these compounds and are performing optimization of compounds in the cooperation with pharmaceutical companies, other universities, and Toyama Prefectural Institute for Pharmaceutical Research to develop novel therapeutics for chronic inflammatory diseases.