Backed by a £3.83 million Wellcome Discovery Award, the ambitious and visionary eight-year programme will focus on understanding and controlling the immune system’s regulatory mechanisms, with a particular focus on the liver. The team will investigate the role of FOXP3+ regulatory T cells (Tregs) in maintaining immune tolerance and preventing tissue damage caused by autoimmune responses.
In October 2025, Professor Sakaguchi alongside US scientists Mary Brunkow and Fred Ramsdell, was announced as a co-winner of the 2025 Nobel Prize in Physiology or Medicine. The Prize was granted for work uncovering how Tregs maintain a healthy balance within the immune system, creating opportunities for new treatments in diseases where immune tolerance is dysregulated.
Autoimmune diseases occur when the body’s immune system mistakenly attacks its own tissues. For liver diseases such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, there is currently no cure. Chronic inflammation promotes organ damage and a loss of function that eventually leads to the requirement for liver transplantation, after which the liver diseases may still recur.
Given this, there is a fundamental need for improved, earlier treatment. Through the expertise of project leader Ye Htun Oo, Professor of Autoimmune Liver Diseases at the University of Birmingham, the team will use a human liver perfusion system to investigate the regulatory potential of a new type of Tregs, developed by Professor Sakaguchi. The function of these cells will be assessed by harnessing the expertise of Professor Graham Anderson, University of Birmingham, in thymic T-cell development and immune tolerance, and Professor Dendrou’s analytical capabilities in autoimmune disease cell and tissue profiling by using multiomic technologies.
Professor Dendrou commented, ‘Through this exciting research programme we aim to initially develop and test our Treg-based approach in the liver and then extend it to other organs and diseases where immune tolerance is broken, such as rheumatoid arthritis, inflammatory bowel disease and type 1 diabetes. Over 25% of patients with one autoimmune disease have a second condition affecting another organ – therefore we need effective approaches to holistically treat the patient – not just any single disease.’
The team is grateful to the Wellcome Trust for funding this exciting research.