Grant: Project Grant - PA: Pandemic Preparedness and Health Emergencies Research

Lungs provide a necessary interface between the body and the environment and require a specialized immune system to respond appropriately to lung-specific pathogens and irritants. Gamma delta (gd) T cells are an important part of the immune system in mucosal barrier tissues, including the lungs. However, under certain conditions gdT cells can escape their normal control mechanisms, causing lung damage and disease. Consequently, there is an urgent need to find ways of boosting gdT cell protective functions and inhibit their harmful functions. We have made the exciting discovery that a protein called Id3 is a critical regulator of gdT cell function. Intriguingly, removal of Id3 appears to split gdT cells into two distinct subsets that could have relevance to health-promoting versus damage-inducing functions. Therefore, we propose to apply our unique insights, new mouse models, and cutting edge technologies to investigate how these gdT cell subsets function in the lung in response disruption in the microbiota ("good bacteria") and to viral infection. Insights obtained from this work should enable significant progress toward the clinical goal of restraining gdT cell-mediated pathology while enabling the gdT-mediated protective immune response.