[Toshiyuki Shimizu] Structural analyses of Toll-like receptors sensing single stranded nucleic acids in innate immunity and their application

Research Director

Toshiyuki Shimizu
Toshiyuki Shimizu
The University of Tokyo



Higher organisms have an immune system for eliminating pathogens to protect themselves. The immune system is composed of two major subdivisions, innate immunity and adaptive immunity. Both systems play crucial roles in the host defense mechanism. The innate immune system is a primary defense mechanism against invading organisms, while the adaptive immune system acts as a second line of defense. Ligands including nucleic acids derived from pathogens trigger strong innate immunity. This is because Toll-like receptors sense the ligands. Four TLR family members have been implicated in nucleic acid recognition: TLR3, TLR7, TLR8, and TLR9. These receptors are localized to endosomes and lysosomes, where they monitor the lumen of these compartments for nucleic acids. We focus on TLR7, 8 and 9 recognizing single stranded nucleic acids and reveal the three-dimensional structures. These TLRs are potential targets for vaccination and control of autoimmune diseases. We aim at therapeutic drug development of these diseases based on the structural knowledge.

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