Sakaguchi, Ramsdell, Rudensky win Crafoord Prize for discoveries in immune regulation

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Three immunology researchers shared the 2017 Crafoord Prize in Polyarthritis “for their discoveries relating to regulatory T cells, which counteract harmful immune reactions in arthritis and other autoimmune diseases.”

Shimon Sakaguchi, of Osaka University, discovered and documented the occurrence of regulatory T cells by systematically investigating cells that develop in the thymus of young mice in a series of experiments from 1985 onwards.

Fred Ramsdell, head of research at Parker Institute for Cancer Immunotherapy, identified the faulty gene in some mice and children that are born with IPEX, a severe autoimmune disease, in 2001. This gene, FOXP3, has proven to be vital in the development of regulatory T cells.

Alexander Rudensky, of Memorial Sloan Kettering Cancer Center, knocked out the FOXP3 gene in mice in 2003, so they were unable to form regulatory T cells and thus suffered from severe autoimmune diseases. At about the same time, Sakaguchi and Ramsdell independently presented evidence that FOXP3 governs the formation of regulatory T cells.

The prize money is 6 million Swedish krona, about $1.3 million. The Crafoord Prize is awarded as a partnership between the Royal Swedish Academy of Sciences and the Crafoord Foundation in Lund. The Royal Swedish Academy of Sciences is responsible for deciding upon the Crafoord laureates.

The prize is awarded in one discipline each year, according to a set schedule for mathematics and astronomy, geosciences, and biosciences.

The prize for polyarthritis is awarded only when a special committee has demonstrated that scientific progress in this field has been such that an award is justified.

According to the prize committee:

“Even back in the 1960s, researchers were searching for suppressor cells in the immune system, but the research results were contradictory. Accordingly, over time, the consensus became that no such cells existed. Despite this, Shimon Sakaguchi persevered with the search and, after many years, he succeeded in identifying the cells that are now called regulatory T cells.

“Some years later, Fred Ramsdell approached the same area from a different direction; he isolated and identified the gene that is linked to severe autoimmune disease in a particular strain of mice. He also demonstrated that mutation in the same gene in humans, now known as FOXP3, causes a severe congenital disease called IPEX. Shortly afterwards, decisive findings were made, linking these two pieces of knowledge together. Alexander Rudensky, Shimon Sakaguchi and Fred Ramsdell each described how the FOXP3 gene is vital to a process that results in some T cells becoming security guards in the immune system. These are the regulatory T cells, which can prevent autoimmune reactions because they detect and suppress overzealous colleagues in the immune system.

“A great number of clinical trials are now being conducted globally, with research teams testing various ways of using regulatory T cells to subdue the immune system’s attacks that cause autoimmune diseases. The long-term vision is that of a breakthrough in the treatment of polyarthritis and other autoimmune syndromes, which could be treated more effectively than they are today.”

The prize will be awarded in Stockholm on May 18.

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