MRC CoRE in Restorative Immunology

Immune-mediated inflammatory diseases (IMIDs) affect people of all ages and can cause lifelong damage to organs such as joints, gut, liver and salivary glands. These conditions are commonly treated with drugs that suppress the immune system, but most individuals never achieve drug-free remission. Instead, most people require lifelong treatment with drugs that increase risk of infections, cancer, and other serious complications, but that fail to address the underlying causes of the disease.
Our ambition is to transform how IMIDs are treated. Instead of only suppressing disease, we aim to develop therapies that restore immune balance and tissue health, achieving true remission without the need for ongoing immunosuppression. To achieve this goal, we will use cutting-edge technologies to define remission, uncover hidden biological mechanisms of inflammation and its resolution in affected tissues and apply advanced therapies to reset the immune system to a state of health. Our approach redefines treatment success; not just improvement in symptoms, but biological remission, measured directly in the tissues where disease occurs. We will build a cellular and molecular atlas of the target tissues of diseases to identify shared pathways of disease resolution, using artificial intelligence and other novel data mining tools, and create a platform to test and translate new therapies that maintain freedom from disease and confer a normal health-span.
This paradigm shift in the treatment of IMIDs is urgently needed, due to the lifelong risk of morbidity and mortality associated with chronic illness, medication toxicity and the considerable economic implications of managing these conditions. Besides the significant healthcare resources and costs devoted to treating these conditions, there are substantial impacts beyond healthcare, including reduced productivity for those who are of working age and the loss of educational and social opportunities for children and young people. As a result, therapeutic approaches that achieve long-term drug-free remission represent an area of unmet clinical need that could be transformative, not just for individual care, but also for wider society.
Recent advances in cellular and molecular engineering, including the ability to selectively deplete, suppress and re-program specific disease-causing cells, are revolutionising cancer outcomes, but their potential as therapies in IMIDs are yet to be fully realised. RESET’s goal is to embrace these therapeutic approaches, alongside detailed molecular analysis of affected tissues, to specifically identify and then target pathways that promote resolution of disease, augment homeostasis and establish sustained drug-free remission. Furthermore, RESET will evaluate the potential cost-effectiveness of these therapies and their strategic application in the current treatment landscape, helping to inform future healthcare policy, in partnership with regulatory bodies.
To realise this vision, our MRC Centre of Research Excellence, RESET, connects a unique network of interdisciplinary and synergistic expertise in data science, tissue immunology, experimental medicine, clinical trial design and health economics, bringing together seven world-leading UK universities, international collaborators, wide-ranging industry and biotechnology partnerships, charities and patient groups. RESET will embrace a unified research culture and team-science ethos across all sites, building a highly collaborative research ecosystem that interfaces with external stakeholders and policymakers. We will train a new generation of translational scientists and clinicians with the skills to address the healthcare challenges of the future.
Our 14-year programme will deliver life-changing new therapies and make drug-free remission a reality for people living with these diseases.