Nordic Life Science 1
MEDICINE // PERIPHERAL IMMUNE TOLERANCE who devel
op fatal multi-organ autoimmune disease within weeks unless they have an allogeneic stem cell transplantation, is due to mutations in the FoxP3 gene,” describes Taskén. “In 2003 Sakaguchi then showed that FoxP3 is the lineage-defining transcription factor that defines Tregs by turning on a specific gene program. These and later findings have led to the development of a whole field,” he says. “There are several mechanisms in place to maintain peripheral immune tolerance, and the findings made by this year’s laureates clearly showed that the absence of FoxP3+ Tregs is enough to break tolerance in both mouse and man,” adds Leo Holmgren, CEO at the Swedish biotech company TIRmed Pharma. Nordic research on Tregs The Nobel laureates revealed that immune tolerance is not established only in the thymus, where immune cells are first “trained”, but that there is also a crucial second layer of control in the body’s peripheral tissues, describes Landegren further. “We are now beginning to see promising developments where Tregs are being harnessed or boosted to treat autoimmune diseases,” he says. Tregs have for example been shown to be clearly involved in a number of autoimmune diseases such as Crohn’s disease, Graves’ disease, and diabetes type I. Landegren and his colleagues have also studied patients with IPEX syndrome to better understand how Tregs prevent the immune system from attacking the body’s own tissues. “We found that these patients develop strong immune responses against several tissue-specific proteins in the gut, which aligns with their severe autoimmune bowel disease. These findings highlight just how essential Tregs are for maintaining immune balance, particularly in the gut,” he explains. In Oslo, at Taskén’s lab, work on Tregs started more than 20 years ago, after his former PhD student, Einar Martin Aandahl, did a post-doc at the Gladstone Institute in San Francisco and then came back to continue his work. “Aandahl also specialized in transplantation surgery for which Tregs and tolerance is very relevant [to diminish the risk of transplant rejection] and he later left to start a company,” he describes. Taskén and his colleagues have also discovered that human Tregs need significantly greater activation to be supNils Landegren, Assistant Professor and Group Leader, Uppsala University and SciLifeLab NORDICLIFESCIENCE.ORG | 29 ILLUSTRATION © THE NOBEL COMMITTEE FOR PHYSIOLOGY OR MEDICINE/MATTIAS KARLÉN PHOTO MIKAEL WALLERSTEDT