People with allergies produce large amounts of IgE antibodies, which circulate in the blood and bind to IgE receptors in mast cells in the lungs, gastrointestinal tract, skin and other organs. Some IgE antibodies recognize specific allergens, including foods, insect venoms, drugs and airborne particles such as pollens and animal danders. Allergic reactions are triggered when mast cell-bound IgE encounters specific allergen, leading to receptor aggregation, mast cell activation, and the release of histamine, prostaglandins, leukotrienes and cytokines. This antigen-driven cross-linking of mast cell-bound IgE is what triggers acute asthma attacks or anaphylaxis.

IgE antibodies can also exert antigen-independent effects. For instance, IgE, even in the absence of allergen, increases the number of IgE receptors, mast cell survival, and cytokine production. Thus high levels of IgE, which are invariably present in allergic individuals, may not only drive acute allergic reactions but also regulate many other aspects of the immune response. Oettgen's studies aim to define the precise molecular and cellular pathways through which IgE antibodies regulate immune functions. A better understanding of the allergic process should enable physicians to more effectively use the new anti-IgE therapies.

IgE antibody production is driven following exposure to allergens, substances which drive allergic responses such as inhaled pollens and dust mites or ingested peanuts. A common thread to allergic responses is the early production of the cytokine, IL-4, following allergen exposure. The Oettgen Laboratory is now investigating whether basophils, which they have observed to appear very early following allergen encounter, might be the critical source of IL-4 driving allergic reactions.

Several years ago, the Oettgen laboratory joined a national consortium of research groups coordinated by the National Institutes of Health, the Atopic Dermatitis Vaccinia Network (ADVN). As part of this network, the lab is studying the pathophysiology of eczema vaccinatum, a severe vaccine side effect in which recipients of small pox vaccine develop a potentially-fatal overwhelming infection with the vaccine strain (vaccinia) virus. Researchers in the Oettgen group have characterized experimental mouse models in which mice with allergic skin inflammation resembling atopic dermatitis develop intense infections following vaccinia exposure based on defective immune responses to the virus. The mechanisms whereby eczema impairs normal immunity to virus in the skin are now being examined.