Mice to Medicine: Unpacking the Nobel-Winning Journey in Immune Regulation

This year’s Nobel Prize for Medicine and Physiology is awarded for groundbreaking discoveries in the field of immunology to Shimon Sakaguchi (Osaka University, Japan), Mary. E. Brunkow (Institute for Systems Biology, Seattle, USA) and Fred Ramsell (Sonoma Biotherapeutics, San Fransico USA.) Their work regarding ‘Peripheral Immune Resistance’ is touted to have opened up new possibilities in autoimmune disorder therapy and cancer research. Beyond the terminologies, let us unpack their discoveries and what it could mean for the future of healthcare.

After a decade long research, Sakaguchi made the first breakthrough in this field in 1993, identifying a new class of T cells (type of white blood cells that help your immune system fight germs) called T regulatory cells (Treg). These cells were theorized to prevent our immune system from attacking and damaging self-cells. Conclusive proof for this discovery, however, came from Brunkow and Ramsdell’s research that offered a potential explanation for the genetic basis of these cells. At the center stage of their work is a mouse strain named Scurfy, a true evolutionary happenstance. While working on the sex-linked human autoimmune disorder IPEX, they took an interest in this particular strain of mouse, that is characterized by enlarged spleen and lymph glands, similar to conditions observed in individuals with IPEX. After laborious studies, in 2001 they determined the root cause to be mutations in a newly uncovered gene called FOXP3. The two findings were pieced together and in 2003, Sakaguchi and other scientists offered definitive evidence that substantiated the control of FOXP3 gene on the development of Treg cells. In precis, this forms our body’s peripheral immune resistance where Treg functions as security guard for body’s self-cells.

These discoveries have direct implications in autoimmune disorder therapy and organ transplantations, wherein promoting Treg cells formation can provide a potentially definitive cure for the former and improve the chances of positive outcome in the latter case. Given that globally about 1 in 5 people are affected by cancer at some point in their lifetime, there’s much anticipation for what it could hold for cancer therapy. One major development is that scientists have deduced the ability of tumour cells to attract large numbers of Treg cells and shield itself from the immune system. Ongoing investigations are focused on how to overcome this barrier of Treg cells. This provides ground for cautious optimism. With their novel discoveries, Sakaguchi, Ramsell and Brunkow have invigorated the field of immunology and healthcare.