Murakami: In order to realize a healthy, long-lived society, it is important to detect "microscopic inflammation" that is the bud of disease at an extremely early stage, and to identify and eliminate those that lead to disease. Young researchers, including graduate students, are working on this basic research every day.


Professor Masaaki Murakami

When our bodies are affected by disease, "inflammation" occurs. Dr. Masaaki Murakami has focused on the mechanism by which inflammation occurs, and has published numerous innovative research results through steady experiments. We have announced the new concept of gateway reflex and IL-6 amplifier, and have clarified the causal relationship between various diseases from the perspective of inflammation. A large-scale project is currently underway to utilize the knowledge gained from basic research to date in medical technology.

Inflammation associated with a wide range of diseases begins with "IL-6 amplifier"

First of all, please tell us what "inflammation" is.

Murakami: Inflammation is a reaction that occurs when immune system cells (hereinafter referred to as immune cells) work to attack and eliminate foreign substances such as bacteria and viruses that have invaded the body. When immune cells gather in large numbers in places where they would not normally exist and become activated, inflammation occurs, causing symptoms such as fever, redness, swelling, pain, and functional impairment.
For example, when you are bitten by a mosquito, the area becomes red and swollen, and when you have an allergic reaction to pollen, this is also inflammation.

Another thing I want everyone to know is that inflammation is involved in a variety of diseases. In addition to colds, toothaches, and allergies, inflammation is actually the starting point for psychiatric illnesses such as Alzheimer's disease and schizophrenia. This is a very important research field.

Dr. Murakami, who has been researching inflammation for many years, has published two innovative research studies so far. The first keyword is "IL-6 amplifier". Please explain

Murakami: The biggest point of the "IL-6 amplifier" announced in 2008 is that it changed the perspective of conventional immune research that focused only on immune cells to "non-immune cells, which had been thought to have no immune function." We discovered that non-immune system cells have a very large influence on the induction of diseases, where microscopic inflammation becomes large chronic inflammation.

"IL-6" (interleukin 6) in "IL-6 Amp" is a type of inflammatory cytokine (a protein produced by immune cells etc. in response to various stimuli).
When non-immune system cells receive specific stimuli such as foreign substances or altered endogenous substances, they release IL-6, and in response, the assembled immune cells also produce the factor. As a result, chemokines, which are chemotactic factors that attract immune cells, and growth factors that increase tissue cells, are rapidly produced, attracting even more immune cells, and releasing more and more IL-6 and chemokines, causing inflammation that was previously minute. progresses to chronic disease.
The mechanism by which IL-6 self-amplifies is called the "IL-6 amplifier," using the word "amplify."

What I would like to focus on here is where the "IL-6 amplifier" is occurring. It is known that there are cells in each organ that are more likely to activate IL-6 amplifiers and cause inflammation, such as the renal tubular epithelium, which is found only in the kidneys, and the basal cells of the bronchial epithelium in the lungs. Therefore, by finding the "IL-6 amplifier," it became easier to pinpoint the location of even minute inflammation.

IL-6 amplifier


Attempting to control the ``gateway reflex,'' a mechanism by which self-reactive immune cells invade organs from blood vessels

It seems that some immune cells attack themselves.

Murakami: That's right. It is known that the number of immune cells that attack us as our destiny increases due to aging and stress. While they remain in the blood, they do no harm, but if they escape from the blood vessels and induce inflammation, they can cause disease.
When neural circuits are activated by various causes such as mental stress, electrical stimulation, light, pain, and gravity, neurotransmitters open tunnel-like passages or vascular gates in blood vessels.
In 2012, we announced the mechanism by which immune cells that pass through this barrier enter tissues, where small inflammations that are the ``buds of disease'' occur, and which spread and lead to disease as the ``gateway reflex.''

It is the ``IL-6 amplifier'' in vascular endothelial cells that causes the ``gateway reflex,'' and it is also the ``IL-6 amplifier'' that increases inflammation after leaving the blood vessel. The clarification of this series of mechanisms has greatly advanced our understanding of autoimmune diseases.

gateway reflection


Aiming to apply these unique research results to medical technology next, Professor Murakami is currently promoting ``moonshot'' challenging research and development based on bolder ideas that are not just an extension of conventional technology. Moonshot type research and development project” as a project manager.

Murakami: Engineering teachers who specialize in quantum technology are also participating in our Moonshot Project. Our future goal is to use quantum technologies such as diamond nanosensors and AI nanopores to detect micro-inflammation, which is caused by excessive self-attacking immune cells gathering in microscopic areas, and which can lead to disease. Detect with high precision.
By using these methods, it may be possible to return to health from the definition of "pre-symptomatic disease," which lies between health and disease.

The micro-inflammation that we discovered will be eliminated by artificially controlling specific neural circuits related to the "gateway reflex" in collaboration with members specializing in neuroscience. Specifically, we are working on the development of technology to reversely close loose blood vessels by applying artificial stimulation such as weak electricity, ultrasound, and magnetic fields to neural circuits.
In this way, we have established technologies for both ``diagnosing diseases'' and ``nipping them in the bud'', and ultimately aim to combine these technologies with information science to turn these technologies into compact devices.

“Micro-inflammation” control project

Application “for the benefit of society” comes from carefully completing the research at hand.

I am amazed at the scale of applied research.

Murakami: The goal of this project is to create a society where everyone can enjoy life without worrying about their health until they are 100 years old, and that is to achieve at least 3 of the 17 goals of the SDGs, ``Good health and well-being for all.'' 9 We believe that this is directly connected to "Let's create a foundation for industry and technological innovation."

future vision

All of these large-scale projects are based on basic research.

Murakami: I would like to say this out loud, but basic research is extremely important. Of course, it is admirable to think, ``I want to use my research for the benefit of society!'' However, if you are only concerned about the exit of society, your perspective will become narrow, and you will be in a hurry and move in the wrong direction. It may happen.

Rather than that, I would be happy if people could understand that looking sincerely at their own genuine questions and interests such as ``Why?'' and carefully conducting experiments is the driving force behind continuing basic research.

Do you have any tips for making your own discoveries like Mr. Murakami?

Murakami: Unfortunately, there are no tips or shortcuts. I was able to discover the ``gateway reflex'' because one day I discovered a single entry point in the blood-brain barrier through which immune cells that attack the body can pass. "Huh? What is this?" I couldn't help but stop.
According to textbooks, immune cells are not allowed to enter the blood-brain barrier. In other words, there are cells where there should be no cells according to conventional wisdom.

At that time, if I had thought to myself, ``What, I made a mistake?'', I think all the clues I had found would have been in vain.
Instead, we repeatedly check whether the results in front of us are correct through accurate experiments. Believe in yourself and carry out experiments carefully. I think this is the only way to arrive at an original discovery.

Therefore, it is time for you to do your best when you get an ``insane result''. Take care of everything in front of you, one by one. Research in the life sciences that affects life inevitably takes time, but if you do it randomly and announce the wrong thing, trust and confidence will be destroyed in an instant. It's the same with human relationships, isn't it?

It is only through basic research that has been carefully accumulated in this way that it develops into good applied research.

Murakami: That's right. At Hokkaido University, I think the most important factor is the clinical faculty at Hokkaido University Hospital, who understand the importance of basic research. Young researchers, including graduate students from various clinical departments who are responsible for daily clinical practice, are currently continuing ambitious research in my laboratory. It is very reassuring that these young researchers will act as a bridge between clinical practice and basic research.

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Masaaki Murakami Professor

Affiliation: Molecular Neuroimmunology Institute for Genetic Medicine Hokkaido University
Group Leader, Quantum Immunology Group, Quantum Life Research Institute, Quantum Technology Research and Development Organization
Professor, Department of Molecular Neuroimmunology, National Institute for Physiological Sciences, National Institutes of Natural Sciences
Visiting Professor, Osaka University Immunology Frontier Research Center

Medicine, immunology, experimental pathology
After graduating from the Hokkaido University School of Veterinary Medicine, he conducted research on IL-6 at the Osaka University Graduate School of Medicine and received a degree. Afterwards, he conducted research on T cells at Hokkaido University, the National Jewish Medical Research Center in Denver, and the University of Colorado, before returning to Osaka University and discovering the IL-6 amplifier and gateway reflex.