Researcher | Research Overview
The Oettgen laboratory focuses on IgE 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 and on the counteracting effects of allergen-specific IgG antibodies in suppressing allergy. The group has found that food-specific IgG antibodies, signaling via the inhibitory Fc receptor, FcgRIIb, block the IgE-mediated activation of mast cells and basophils and promote the emergence of regulatory T cells. Food specific IgG is strongly induced by oral immunotherapy and these results suggest that this IgG may mediate the beneficial effects of this treatment and that allergen-specific IgG might eventually prove to be a useful therapy.
Oettgens' studies aim to define the precise molecular and cellular pathways through which IgE and IgG antibodies regulate immune functions. A better understanding of the allergic process should enable physicians to more effectively use the new anti-IgE therapies.
Researcher | Research Background
Dr. Oettgen received his MD from Harvard Medical School along with a PhD in Immunology, training with Cox Terhorst, PhD. He completed his clinical training in Pediatrics and Allergy & Immunology at Boston Children’s Hospital and did post-doctoral laboratory studies with Dr. Philip Leder, Chair of Genetics at Harvard Medical School. Upon completion of his training, he was selected as a recipient of a Pew Scholarship and started his research laboratory, which has been consistently NIH-funded, at Boston Children’s Hospital. He represents the Hospital as one of the core researchers in the Food Allergy Science Initiative (FASI) based at the Broad Institute in Cambridge where he is an Associate Member. He will co-chair the upcoming Gordon Research conference on Food Allergy to be held in Ventura, California in January 2022. 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.
- Kanagaratham C, El Ansari YF, Salis BF, Hollister BA, Lewis OL, Minnicozzi SC, Oyoshi MK, Rosen R, Nurko S, Fiebiger E, Oettgen HC. Omeprazole inhibits IgE-mediated mast cell activation and allergic inflammation induced by ingested allergen in mice. J Allergy Clin Immunol. 2020;146:884-893. PMID: 32194041
- Turner JA, Stephen-Victor E, Wang S, Rivas MN, Abdel-Gadir A, Harb H, Cui Y, Fanny M, Charbonnier LM, Fong JJH, Benamar M, Wang L, Burton OT, Bansal K, Bry L, Zhu C, Li QZ, Clement RL, Oettgen HC, Crestani E, Rachid R, Sage PT, Chatila TA. Regulatory T cell-derived TGF-β1 controls multiple checkpoints governing allergy and autoimmunity. Immunity. 2020;53:1202-1214. PMID: 33086036
- Burton 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