Gene-regulatory functions of TOX in the immune system

T cells are a type of white blood cell that play a central role in vertebrate immune systems by attacking germs and killing unhealthy cells, making T cells the primary defence against many infections and diseases. To enable protective immunity against a wide range of pathogens, T cells can adopt specialized differentiation and activation states, which equip them to fight off foreign invaders. However, when T cells encounter long-lasting threats such as chronic viral infections or cancer, they become "exhausted", losing some of their effectiveness. This state of reduced activity is likely controlled by self-sustaining gene regulation pathways, which make the treatment of various diseases including cancer difficult. The transcription factor TOX is a central regulator of this exhaustion process in T-cells, but its precise mechanism of action is still a mystery. The proposed study will fill this gap by investigating both the functional roles and genetic regulation of TOX. This transcription factor has different roles in different parts of the immune system: in the early stages of T cell development, and in supporting T follicular helper cells specialised T cells which assist in antibody production and immune memory formation for effective defence against pathogens. TOXs diverse roles make it a critical component to understand how our immune system really works.

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