The aim of this project is to understand how Fc receptors communicate intracellular signals to initiate mast cell activation leading to inflammation. Fc receptors are key players in autoimmune diseases like systemic lupus erythematosus and in allergic disease. We have focused on signaling proteins that may serve as possible links from Fc receptor to gene expression and mast cell degranulation and on how this receptors activity is regulated. This focus is based on increaing the knowledge of potential therapeutic targets in autoimmune and allergic disease. Results: The objectives of the past year were met in the following manner. First, studies on how the IgE receptor can distinguish between high and low affinity antigens were initiated as well as studies aimed at therapeutic intervention in mast cell function. These studies led us to explore the use fo adaptor molecules in mast cells and showed that the difference in affinity is interpreted into different usage of molecular signaling pathways. In addition, our studies using a parental compound that disrupts lipid raft integrity has demonstrated that such compounds inhibit mast cell degranulation. Additional work explored whether other stimuli that lead to mast cell activation functioned through the use of Lyn or Fyn. This work demonstrates that depending on the stimulus dominance of kinase usage may differ. Conclusions and Significance: In summary, our findings support the view that different stimuli can elicit specific responses through the use of particular molecular signaling modules. These findings provide new avenues for future exploration toewards understanding the role of IgE Fc receptors in health and disease.
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