Accurate discrimination between self and non-self molecules and robust tolerance against self molecules is the key to prevent autoimmunity. However, effective self-tolerance can also limit immunological defense against tumors. Thus, detailed molecular understanding of how the immune system defines self vs. non-self can guide therapeutic strategies for cancer immunotherapy as well as autoimmune disease. One protein that plays an important role in establishing self-tolerance in T cells is Aire. This protein causes thousands of self-antigens to be expressed in the thymus so that self-reactive T cells can be deleted and immunosuppressive regulatory T cells can develop.
Despite its importance, exactly how Aire regulates expression of self-antigens remains poorly understood, so Dr. Kazuki Kato aims to dissect its molecular mechanisms. He recently discovered that Aire directly binds Cyclin C, which itself is a poorly understood of a complex called Mediator. Using a combination of advanced techniques, Kazuki will be investigating if this Aire-Cyclin C interaction plays a key role in Aire-mediated expression of self-antigens in thymus. Overall, his work may offer a new platform to further dissect the thus far elusive mechanism of Aire as well as also reveal previously unrecognized functions of the Mediator complex.
Projects and Grants
Molecular Mechanism of Auto-Immune Regulator (Aire)
Boston Children’s Hospital | All Cancers | 2020 | Sun Hur, Ph.D.
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