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 growth and function of mast cells in the intestine. They are also studying how IgE and mast cells regulate 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 release of mediators is what causes allergic reactions to foods including anaphylaxis.
IgE antibodies can also exert effects in the absence of allergen encounters. For instance IgE, by itself, 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. The Oettgen lab has recently focused on the role of IgE antibodies and mast cells in immune regulation. Using novel mouse models of peanut allergy developed in collaboration with Dr. Talal Chatila, also in the Division of Immunology, they have demonstrated that mast cells, activated by IgE, suppress the induction of regulatory T cells and promote the induction of the pro-allergic subset of T-helper cells known as Th2 cells. The group is now testing whether interference with IgE:mast cell activation during food ingestion in an allergic host will allow regulatory mechanisms to take hold and eliminate established food allergies.
Oettgens' 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.
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.
OT, Noval Rivas M, Zhou JS, Logsdon SL, Darling AR, Koleoglou KJ, Roers
A, Houshyar H, Crackower MA, Chatila TA, Oettgen HC. Immunoglobulin E
signal inhibition during allergen ingestion leads to reversal of
established food allergy and induction of regulatory T cells. Immunity. 2014 Jul 17;41(1):141-151. PMID: 25017467
- Burton OT, Logsdon SL, Zhou JS, Medina-Tamayo J, Abdel-Gadir A, Noval Rivas M, Koleoglou KJ, Chatila TA, Schneider LC, Rachid R, Umetsu DT, Oettgen HC. Oral immunotherapy induces IgG antibodies that act through FcyRIIb to suppress IgE-mediated hypersensitivity. J Allergy Clin Immunol. 2014 Dec;134(6):1310-1317. PMID: 25042981
SL and Oettgen HC. Anti-IgE therapy: clinical utility and mechanistic
insights. Curr Top Microbiol Immunol. 2015;388:39-61. PMID: 25553794