This year's Nobel Prize in Physiology and Medicine was awarded to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi for their discoveries concerning peripheral immune tolerance and regulatory T cells. These immune cells play an important role in protecting us from autoimmune diseases, and key to their development and function is the transcription factor FOXP3.

In 1995, Sakaguchi and colleagues were the first to show that immune tolerance, i.e. the prevention of an immune response to certain antigens, such as those present on our own bodies, is not only established by clearance of developing autoreactive immune cells in the thymus and bone marrow. While such central immune tolerance had long been recognized, Sakaguchi et al. demonstrated that there is also a peripheral mechanism mediated by a specific class of T cells, naming them regulatory T cells (Sakaguchi, 1995).

In 2001, Brunkow and Ramsdell published an article describing the gene FOXP3, the disruption of which caused excessive proliferation of B- and T cells, and thus multiorgan immune infiltration in mice (Brunkow, 2001). FOXP3 is highly conserved in humans, and mutations are associated with a rare immune disease called IPEX (Immunodysregulation polyendocrinopathy enteropathy X-linked) syndrome (Bennett, 2001). Two years later, Sakaguchi's team showed that FOXP3 is a transcription factor that governs the development of regulatory T cells.

In the Subcellular resource of the Human Protein Atlas, FOXP3 mainly localizes to the nucleus. It can act as a transcriptional repressor or activator depending on its interaction with other proteins, such as chromatin modifiers, to induce the expression of anti-inflammatory genes and repress the expression of proinflammatory genes, as well as maintaining the phenotype of regulatory T cells (Vent-Schmidt, 2014).