Nobel Prize in Physiology/Medicine 2025

Last week saw the announcements of the 2025 Nobel Prize winners, and the prize for Physiology or Medicine was shared between three researchers “for their discoveries concerning peripheral immune tolerance”: Mary E. Brunkow; Fred Ramsdell; and Shimon Sakaguchi.

In 1995, Sakaguchi discovered regulatory T cells (or Tregs), described their role in protecting the body from autoimmune responses and a mechanism by which this occurs. Rate and review:

Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases

Abstract Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in normal unimmunized adult mice express the IL-2 receptor α-chain (CD25) molecules. When CD4+ cell…

PaperstarsS Sakaguchi, N Sakaguchi, M Asano, M Itoh, M Toda

Then in 2001, Brunkow and Ramsdell identified the FOXP3 gene, which is essential for typical Treg development and function. They knocked out Foxp3 in mice which resulted in severe autoimmune disease and identified a specific mutation that causes IPEX syndrome in humans. This provided the generic mechanism that controls the cells which Sakaguchi discovered. Rate and reveiw:

A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA→AAUGAA) leads to the IPEX syndrome

PaperstarsCraig Bennett, Mary Brunkow, Fred Ramsdell, Kathy O’Briant, Qili Zhu, Ramsay Fuleihan, Ann Shigeoka, Hans Ochs, Phillip Chance

Earlier this year, Sakaguchi published a genome-wide screen in human Tregs, identifying novel regulators of FOXP3, laying the groundwork for future work in improving therapies for autoimmune disease. Rate and review below:

Genome-wide CRISPR screen in human T cells reveals regulators of FOXP3

Paperstars

This Nobel Prize showcases the efforts of these three scientists over the last three decades and highlights the importance of collaboration in the search for scientific discovery.