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Mechanisms that underlie loss of antigen tolerance in HLA-associated autoimmune diseases

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HLA molecules in autoimmune diseases

European researchers dissected the arm of the immune system that is responsible for autoimmune diseases (AID). They concentrated on specific receptors on antigen presenting cells and their role in inducing and regulating autoimmunity.

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In AID, our body recognises 'self' antigens as foreign thereby leading to destructive inflammatory responses in various organs. Normally our regulatory T cells counteract effector T cells through a phenomenon called antigenic tolerance, which prevents such adverse effects. To maintain or induce such tolerance, antigen presentation on specialised receptors called major histocompatibility (MHC) or human leukocyte antigen (HLA) class II receptors is required. The precise mechanisms underlying antigen tolerance are poorly understood. The EU-funded 'Mechanisms that underlie loss of antigen tolerance in HLA-associated autoimmune diseases' (IMMUNE TOLERANCE) project worked on elucidating these mechanisms as well as AID. To achieve their goal, scientists used a mouse model of human autoimmune pancreatitis (AIP) to study the role of risk HLA type-restricted T cells in disease induction. They observed that upon adoptive transfer of risk HLA type-restricted T cells animals did not develop AIP, demonstrating that these T cells are not directly causing the disease. Instead, cytotoxic T cells were causing AIP upon adoptive transfer. These results suggested a defect in regulatory T cells restricted by the risk HLA type, underscoring the importance of HLA class II in the predisposition to autoimmunity. Additionally, researchers studied the role of HLA receptors in coeliac disease and evaluated the effectiveness of oral enzyme therapy in a pre-clinical mouse model. Overall, the IMMUNE TOLERANCE study provided invaluable insight into the mechanism of interaction between regulatory and effector T cells in health and disease. Importantly, the work entailed an important translational component by testing the therapeutic potential of enzyme therapy in coeliac disease.


Autoimmune disease, regulatory T cells, effector, human leukocyte antigen, autoimmune pancreatitis, celiac disease, enzyme therapy

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