T helper lymphocytes are of two different types, called T helper 1 and T helper 2. They are defined in that manner because they make different kinds of small polypeptide mediators, called cytokines. It is clear that T helper 1 cells contribute to and worsen autoimmunity, while T helper 2 cells improve autoimmunity. Recent work suggests that dendritic cells of the innate immune system, contribute significant polarizing influences on the development of the T helper types. Most recently, it has been shown that dendritic cells play a crucial role in the development of inflammatory arthritis. Furthermore, this dendritic function is controlled by a novel gene, called T-bet, which was isolated in Dr. Wang’s laboratory. In an inflammatory arthritis mouse model, dendritic cells expressing T-bet cause arthritis. Therefore, T-bet provides an attractive new target for the development of novel therapeutics for inflammatory arthritis.
Dr. Wang will use systemic approaches to analyze how T-bet exerts its function. Various approaches, including genetically mutated mice, will be utilized to identify potential target genes for T-bet in dendritic cells. He anticipates gaining a better understanding of the mechanisms of T-bet function in dendritic cells. These studies may permit the design of therapeutic agents that manipulate the relevant signaling pathways in dendritic cells to control inflammation with much higher efficiency.