Manipulation of signaling to control allergic inflammation

Inflammatory mediators produced from activated mast cells and T helper type 2 cells drive allergic inflammation. The pathways required for mast and T helper type 2 cell activation and the effects of their products are being defined in order to identify new therapeutics. We focus on recent findings on the chief inducer of mast cell activation, the IgE receptor-signaling cascade, and the development of new inhibitors of this pathway. We also summarize work that examines the molecular mechanisms utilized by the interleukin IL-4/13 receptors and characterizes therapeutic compounds that target these pathways.

The tyrosine kinases Lyn, Fyn and Syk have complex roles in IgE receptor signaling. Biochemical analysis and gene expression profiling have shed light on both the positive and negative functions of these proteins and establish additional connections with downstream pathways. Syk inhibitors were identified that may prove useful as antiinflammatory agents. Progress has been made in characterizing how IL-4/13 interact with their cognate receptors that will aid in the design of inhibitors of these interactions.

Recent studies have advanced our understanding of how the IgE receptor and IL-4/13 receptors function. This new knowledge may lead to the development of novel and highly specific inhibitors of allergic inflammation.