The Oettgen laboratory focuses on IgE--the antibody that mediates allergic reactions--and its influence on mast cells, which produce cytokines--chemicals involved in the inflammatory response. The team is currently examining the effects of IgE levels on the growth and function of mast cells of the intestine. They are also studying how IgE regulates immune sensitization in the intestine in the setting of food allergy.
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 allergic reactions to foods including 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.
The Oettgen laboratory is part of a national consortium of research groups coordinated by the National Institutes of Health, the Atopic Dermatitis Research Network (ADRN). 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.
About Hans Oettgen
Dr. Oettgen graduated from Harvard Medical School and completed his internship, residency, and clinical fellowship in Allergy & Immunology at Boston Children’s Hospital. He did his post-doctoral laboratory training with Dr. Philip Leder in the Department of Genetics at Harvard Medical School. Dr. Oettgen holds the Children’s Hospital Boston Professorship in Pediatric Immunology at Harvard Medical School and serves as Associate Chief of the Division of Immunology at Boston Children’s. In addition to directing the Oettgen lab he oversees the clinical programs of the Division, which provides services to children with allergies, immune deficiencies, rheumatologic diseases and skin disorders.
- Burton OT, Oettgen HC. Beyond Immediate Hypersensitivity: Evolving roles for IgE antibodies in immune homeostasis and allergic diseases. Immunol. Rev. 2011;242:128-43.
- Mathias CB, Hobson SA, Garcia-Lloret M, Lawson G, Poddighe D, Freyschmidt EJ, Xing W, Gurish MF, Chatila TA, Oettgen HC. IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling. J Allergy Clin Immunol. 2011;127:795-805.
- Freyschmidt E-J, Mathias CB, Diaz N, MacArthur DH, Laouar A, Manjunath N, Hofer MD, Wurbel M-A, Campbell JJ, Chatila TA and Oettgen HC. Skin inflammation arising from cutaneous Treg deficiency leads to impaired viral immune responses J Immunol. 2010;185:1295-302.