Keystone Conference: Mast cells in physiology, host defense and disease-beyond IgE Summary: Mast cells are a critical source of mediators that contribute to acute allergic reactions. In this setting, mast cell activation via the cross-linking of high affinity receptors for IgE (Fc-epsilonRI) results in the release of preformed molecules (such as histamine), as well as the new synthesis and release of cytokines, chemokines and leukotrienes and prostaglandins. However, mast cells can also be activated via immune complexes, complement products, neuropeptides, cytokines and products of pathogens (e.g., via toll-like receptors). This knowledge has greatly expanded our view of the potential functions of the mast cell in host defense and disease as well as in non-immunological processes such as regulation of epithelial barrier function and modulation of peripheral nerve and cardiac function. This conference will assess what is currently known about the roles of mast cells and will consider how our understanding can be advanced by the application of new technologies and approaches to analyze and manipulate mast cell function. Specifically, the conference will include presentations on: 1. Mast cells as effectors of the leukocyte recruitment and chronic tissue remodeling of asthma and other IgE associated allergic disorders; 2. Mast cells as amplifiers and effectors of IgG and immune complex-mediated disorders, including autoimmune diseases; 3. Mast cells as key contributors to innate and acquired immunity; and 4. Contributions of mast cells to physiology and homeostasis. In addition, the conference will have sessions on: 5. The use of microarray-based, and other, approaches to define the full spectrum of mast cell-derived mediators and other products (and how such information can be used to clarify the roles of mast cells in vivo); 6. Elucidating, at the molecular level, the positive and negative regulation of mast cell development and function; and 7. The development of definitive models for analyzing mast cell function in vivo.