Nobel Prize in Physiology or Medicine 2023
The Nobel Prize in Physiology or Medicine was awarded to Japanese scientist Shimon Sakaguchi and American scientists Mary E. Brunkow and Frederick Ramsdell for their discoveries on peripheral immune tolerance, crucial for understanding immune system functioning and developing therapies for cancers and autoimmune diseases.
Discovery of Peripheral Tolerance
- Researchers had long questioned how the immune system attacks pathogens without harming the body's own cells.
- By the 1980s, central tolerance was known to eliminate T cells that recognize the body's own proteins.
- Sakaguchi introduced the concept of regulatory T cells in 1995, which prevent other T cells from attacking the body’s own cells, a process called peripheral tolerance.
Sakaguchi's Experiments
- Surgically removed the thymus of newborn mice to induce fewer T cells and a weaker immune system.
- Mice developed autoimmune diseases when thymus removal occurred three days post-birth.
- Injected T cells from healthy mice into thymus-less mice, preventing autoimmune conditions.
- Sakaguchi proved the existence of T cell “police” with regulatory functions.
Breakthrough by Brunkow and Ramsdell
- Investigated scurfy mice with autoimmune diseases.
- Narrowed down mouse DNA to 500,000 nucleotides, identifying 20 potential genes.
- Identified the FOXP3 gene as causing autoimmunity in scurfy mice and human IPEX disease.
- Sakaguchi later showed FOXP3 controls regulatory T cells development.
Significance of Discoveries
- Understanding regulatory T cells' role in cancer immunity.
- Regulatory T cells can protect tumors by preventing other T cells from attacking them.
- New cancer immunotherapies and Car-T cell therapy aim to reduce regulatory T cells' action for effectiveness.
- Potential autoimmune conditions as a side effect of these therapies.
- Research on promoting regulatory T cells formation in autoimmune conditions and organ transplant rejection prevention.
- Exploration of modifying T cells to calm overactive immune systems.
The discoveries provide a foundation for innovative treatments and a deeper understanding of immune system complexities.