Citation for the Award

The ability to distinguish between self and non-self is a fundamental principle that is apparent　in all forms of life. For example, in microbes, restriction enzymes cleave foreign DNA to protect the microbes, and the CRISPR-Cas system remembers the genetic information of foreign substances and attacks them; plants have a self/non-self recognition mechanism that maintains diversity by controlling which pollen is accepted; and in animals, the removal of dead cells and rejection of transplanted organs are based on similar principles of recognition. The ability to distinguish between self and other is also an important factor at the level of social behavior and groups. It is essential for living organisms to be able to accurately distinguish between themselves and disease-causing pathogens such as bacteria and viruses, and that is how immune systems – the body’s defense mechanism – function effectively.

However, for a long time it was unclear what molecular mechanisms enabled living organisms to identify pathogens and immediately initiate defensive responses. The innate immune system plays a crucial role here as the body's first line of defense, responding immediately to pathogen invasion to prevent the spread of infection even when antibodies are absent. A fundamental challenge for immunologists to solve was how the innate immune system recognizes pathogen-derived nucleic acids such as DNA and RNA (molecules carrying genetic information) as foreign substances. Professor Shizuo Akira and Professor Zhijian Chen provided a definitive answer to this difficult question. The two scientists successively identified the key innate immune system molecular sensors for nucleic acid recognition (i.e. the receptor proteins that detect foreign substances) and the downstream signaling pathways. Their research has completely revolutionized our overall understanding of innate immunity and has directly contributed to the clarification of the pathogenesis of autoimmune diseases and to the development of new vaccines and immunotherapies.

Akira’s research into toll-like receptors (TLRs), a class of receptors that are responsible for innate immunity in mammals, led to his discovery of TLR9 (2000), which recognizes bacterial DNA-specific unmethylated CpG sequences, and TLR7 (2002), which recognizes viral RNA. Through his work he was able to demonstrate for the first time how innate immunity directly recognizes nucleic acids to induce a defense response during early infection. In addition, he was able to clarify the function of RIG-I-like receptors (RIG-I and MDA5), which are cytoplasmic pattern recognition receptors that detect viral RNA, and show that they are essential for the production of type-I interferons (the primary pathway in antiviral response). He also discovered that intracellular DNA induces immune responses independently of TLRs, which laid the foundation for research into the part of the DNA response system later determined to be the cGAS pathway. These discoveries have been applied widely in research into autoimmune diseases and in the development of vaccine adjuvants (ingredients added to vaccines to enhance immune response), and made a significant contribution to the successful development of mRNA vaccines.

In 2005, Chen identified the mitochondrial antiviral signaling protein (MAVS), a protein that transmits antiviral signals in response to infection by a virus, and systematically clarified the pathway that leads from the detection of intracellular RNA to the production of type-I interferons. He also discovered the sensor molecule that directly senses cytoplasmic DNA in 2013, cGAS (cyclic GMP-AMP synthase), in addition to its second messenger reaction product cGAMP (cyclic GMP-AMP), and the downstream “stimulator of interferon genes” or STING pathway that regulates the response. This revealed the fundamental principles underlying the defense mechanism against infection by DNA viruses, and researchers are now exploring how they can be applied in cancer immunotherapy. Remarkably, a cGAS-like DNA recognition system called the cyclic-oligonucleotide-based anti-phage signaling system (CBASS) was recently found to exist in bacteria, demonstrating that nucleic acid recognition mechanisms are an evolutionarily conserved and universal innate immune strategy.

The complementary research of these two professors has opened new frontiers in the unexplored field of nucleic acid recognition in innate immunity, and broken new ground in infectious disease research, immunology, and vaccine technology.

It is for these reasons that we believe the achievements of Professor Shizuo Akira and Professor Zhijian Chen make them worthy of recognition as the recipients of the 2026 Japan Prize honoring achievements in the field of Life Sciences.