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Regulatory T-cells: Friends or Foes

Humankind chooses to explore not because it is easy, but because it is hard. These journeys fine-tune our energies and skills while leading us into unknown lands and spaces, in the meantime creating new technologies and finding cures for diseases. It is these challenges which we accept, that once won, shapes us as a race. At the La Jolla Institute our collective goal is to understand what we are made of—specifically how immune cells work and interact—and use this knowledge base as a tool to treat not one patient at a time, but thousands.

Cancer, atherosclerosis, autoimmunity, HIV, allergy, and viral/bacterial infections are just a sampling of the complex illnesses we fight. Common to all is the presence of regulatory T-cells, which since their discovery in 1998 still are largely a black box today. Evolution shaped this cell type to naturally shut down the immune system after an infection clears to ensure host survival. However, in the modern era of age-related disease the presence or absence of regulatory T-cells is a double-edged sword. Tumors specifically recruit and mobilize these regulatory T-cells to evade the immune response and efficacy of bioengineered clinical immunotherapies. Conversely, complete absence or dysfunction of regulatory T-cells results in an overactive immune system observed in autoimmune disease.

After investigating over 30 molecular signaling pathways, this initial research identified two key soluble protein immune mediators, IL-12 and TGF-β, act in concert dictating the genetic landscape of regulatory T-cells in the context of inflammation. These findings unveil that this cell type behaves in new ways never before imagined and also further advance core T-cell signaling research programs of other labs at the Institute. As academics, we are the only scientists that dare ask questions to explore the unknown deeper. Understanding how these identified upstream proteins control complex gene expression patterns in regulatory T-cells will unveil new therapeutic avenues and modify existing treatments to better define and give us control over these potent and incredibly relevant cells.