Back in the 1980s, when Shimon Sakaguchi was a young researcher in immunology, he found it difficult to get his research funded. Now, his pioneering work which explains how our immune system knows when and what to attack, has won him a Nobel prize.
Sakaguchi, along with American researchers Mary Brunkow and Fred Ramsdell, were jointly awarded the 2025 Nobel prize in physiology or medicine for their work on regulatory T-cells, known as T-regs for short, a special class of immune cells which prevent our immune system from attacking our own body.
In this episode of The Conversation Weekly podcast, Sakaguchi tells us about his journey of discovery and the potential treatments it could unlock.
Sakaguchi was inspired by an experiment involving newborn mice conducted by his colleagues at the Aichi Cancer Center Research Institute in Nagoya. ?They’d removed the thymus from mice three days after they were born. It was already known that the thymus is important in the development of immune self-tolerance: it’s where T-cells, a type of lymphocyte or white blood cell, that could attack the body are isolated and destroyed. Sakaguchi was intrigued by what happened. He said that if you remove the thymus in a normal mouse in the neonatal period, you would expect immune deficiency because the lymphocytes are gone.
But what happened is just the opposite: they developed autoimmune diseases. ?This disease is very similar to what we see in humans … but of course, human patients are not removed of the thymus, so there must a common mechanism, which can explain spontaneous autoimmune diseases in humans.
Sakaguchi ?decided to try a new experiment to stop the mice’s immune system going into overdrive. When he took some T-cells from genetically identical mice and injected them back into the mice who’d had their thymus removed, he found that autoimmune disease can be prevented. “?This suggests that there must be a T-cell population which can prevent disease development,” he said.
In the 1980s, Sakaguchi said it was not easy to get research funding “because the immunology community were very sceptical about the existence of such cells”. He spent time in the US and he says he was “very fortunate” to be supported by a grant from a private foundation.
After ten years of looking, he published a paper in 1995 setting out his discovery of regulatory T-cells, which act as the body’s security guard, controlling any adverse reactions and keeping the immune system in balance in a process called peripheral tolerance. When these T-regs don’t work properly, this can cause autoimmune diseases. Later work by Sakaguchi, and his fellow laureates Brankow and Ramsdell, discovered the specific gene, called Foxp3 that controlled T-regs.
Cancer, auto-immune treatments and more
When Sakaguchi started out, his interest was in autoimmune diseases and how they occur. “But in the course of my research we have gradually understood that T-regs are more important,” he says. These cells are now implicated in the way cancer attacks the body, as well as the acceptance of organ donations. Sakaguchi is also working on new ways to harness T-regs for treatment, and also on converting other, attacking types of T-cells, into T-regs to target specific autoimmune diseases.
His immediate hope is that some of the clinical trials for cancer immunotherapy can become a reality for treating patients. But he’s also fascinated by recent research which shows the importance of T-regs in diseases which cause inflammation – and what this could mean for potential to repair damaged tissue.
Neuro-degenerative diseases such as Alzheimer’s disease or Parkinson’s disease, all involve inflammation. By just targeting that kind of inflammation, we maybe [could] stop the disease progressions, or delay the disease progression. We hope that it is very true and then it really works for such diseases.
Listen to the interview with Shimon Sakaguchi on The Conversation Weekly podcast.
This episode of The Conversation Weekly was produced by Mend Mariwany and Katie Flood and is hosted by Gemma Ware. Mixing and sound design by Michelle Macklem and theme music by Neeta Sarl.
Listen to The Conversation Weekly via any of the apps listed above, download it directly via our RSS feed or find out how else to listen here. A transcript of this episode is available on Apple Podcasts or Spotify.
Shimon Sakaguchi is the scientific founder and a director of RegCell, a Japanese start-up working on treatments based on regulatory T-cells. He is also a scientific advisor for biotechnology company Coya Therapeutics.
