Type I interferons are a powerful cytokine family that play an essential role in innate immune protection from viruses. In addition to their direct anti-viral activities, they strongly activate multiple cells of the adaptive immune system, including APC, B cells, and T cells. Interestingly, interferons are expressed in the thymus in the steady state, in the absence of infections. In this project, we propose to systematically define the role that thymic type I interferon plays in immunological self-tolerance. We hypothesize that type I interferons are critical to promote tolerance to self-epitopes that are usually only displayed during infections.
Aim 1 will determine what stimuli promote thymic medullary epithelial cells to produce IFNb.
Aim 2 will determine the consequences of IFNb expression on tolerance to conventional and inflammation induced self antigens.
Aim 3 will determine if autoimmunity results in the absence of thymic IFNb, particularly when mice are challenged by infections.
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