Grant: Operating Grant

The human body fights off infections by using a wide variety of white blood cells to kill invading germs ('microbes'). One type of white blood cell is a CD4 T helper (Th) cell that patrols the blood and tissues. Once CD4 Th cells encounter a foreign microbe, they can develop into one of several types of activated cells including Th1, Th2 or Th17 cells. This 'choice' is absolutely critical as each type of cell has a different function in the body- Th1 cells kill bacteria and viruses, Th2 attack worm parasites and Th17 cells control fungal infections. In addition, uncontrolled or inappropriate Th cell responses result in disease. For example, Th1 cells can cause inflammatory diseases like arthritis, Th2 cells are the main cause of asthma and allergies and Th17 cells are associated with Multiple Sclerosis. Thus, the control of this choice is critical for both killing infections and not developing diseases. The focus of this proposal is to understand how this choice is made. I have identified two molecules called G9a and Set7 that play an important role in this decision process. G9a and Set7 act by modifying other proteins and affecting their functions. In the absence of G9a, Th cells can not become Th2 cells. This is a good thing if you have asthma or allergies but a bad thing if you are infected with a worm parasite. In direct contrast, Set7 is critically required for Th1 responses. How G9a and Set7 control this choice is completely unknown and is the major focus of this proposal. The results from these studies will shed light on this important yet poorly understood question and may identify new drug targets that could possibly aid in the treatment of asthma and other allergies.