Transcriptional control of innate T cell effector functions.
A functional immune system is dependent upon a wide variety of lymphocytes, such as T cells and B cells, and myelocytes, such as macrophages and dendritic cells. Specialization of function of these various cell types is fundamental for both successful immune responses against pathogens and for immunosurveillance against cancer. Our lab is interested in 1) understanding the factors that control lymphocyte development and 2) determining if these factors can used to modify or enhance T cell responses against cancer.
Innate T cells, such as natural killer T cells (NKT cells), are extremely potent "first responders" to infection. The aggressive nature of innate T cells has also made them attractive targets for immunotherapy - several clinical trials are in progress. Our lab has recently identified a BTB-ZF transcriptional repressor that controls the development of the innate T cells. In the absence of this factor, innate T cells default to the conventional CD4 T cell lineage. Alternatively, conventional T cells are redirected into the innate T cell lineage by ectopic expression of the transcription factor.
We are working to discover what genes are being repressed by this BTB-ZF transcription factor; how the factor mediates suppression; signaling events that lead to the factor being expressed specifically in innate T cells and control of the expression of the transcription factor. Furthermore, we are determining if redirected expression of the BTB-ZF gene will enhance the activity of conventional T cells.
Finally, we are interested in learning if spontaneous expression of the factor in conventional T cells can lead to autoimmunity.