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Oettgen Laboratory Research

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.

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.

Selected Publications

  1. 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
  2. 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
  3. 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
  4. 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

Education

Undergraduate School

Williams College
1980 Williamstown MA US

Medical School

Harvard Medical School
1987 Boston MA US

Internship

Boston Children's Hospital
1988 Boston MA US

Residency

Pediatrics Boston Children's Hospital
1990 Boston MA US

Fellowship

Allergy & Immunology Boston Children's Hospital
1993 Boston MA

Publications

  1. T follicular helper cell expansion and hyperimmunoglobulinemia with spontaneous IgE production to dietary antigens in IgA-deficient mice. Mucosal Immunol. 2025 Jan 15. View Abstract
  2. Allergen-specific IgA and IgG antibodies as inhibitors of mast cell function in food allergy. Front Allergy. 2024; 5:1389669. View Abstract
  3. Rethinking Immunological Risk: A Retrospective Cohort Study of Severe SARS-Cov-2 Infections in Individuals With Congenital Immunodeficiencies. J Allergy Clin Immunol Pract. 2023 11; 11(11):3391-3399.e3. View Abstract
  4. Rethinking immunologic risk: a retrospective cohort study of severe SARS-CoV-2 infections in individuals with congenital immunodeficiencies. medRxiv. 2023 Jun 05. View Abstract
  5. IgG:Fc?RIIb signals block effector programs of IgE:FceRI-activated mast cells but spare survival pathways. J Allergy Clin Immunol. 2023 08; 152(2):453-468. View Abstract
  6. Mast cells in food allergy: Inducing immediate reactions and shaping long-term immunity. J Allergy Clin Immunol. 2023 01; 151(1):21-25. View Abstract
  7. Allergen-Specific IgA Antibodies Block IgE-Mediated Activation of Mast Cells and Basophils. Front Immunol. 2022; 13:881655. View Abstract
  8. High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy. Cell Rep Med. 2021 10 19; 2(10):100410. View Abstract
  9. Immune changes beyond Th2 pathways during rapid multifood immunotherapy enabled with omalizumab. Allergy. 2021 09; 76(9):2809-2826. View Abstract
  10. Mast Cells as Regulators of Adaptive Immune Responses in Food Allergy. Yale J Biol Med. 2020 12; 93(5):711-718. View Abstract
  11. Regulatory T Cell-Derived TGF-ß1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity. Immunity. 2020 Dec 15; 53(6):1331-1332. View Abstract
  12. IgE and IgG Antibodies as Regulators of Mast Cell and Basophil Functions in Food Allergy. Front Immunol. 2020; 11:603050. View Abstract
  13. Preventing asthma in high risk kids (PARK) with omalizumab: Design, rationale, methods, lessons learned and adaptation. Contemp Clin Trials. 2021 01; 100:106228. View Abstract
  14. IgE and mast cells: The endogenous adjuvant. Adv Immunol. 2020; 148:93-153. View Abstract
  15. Regulatory T Cell-Derived TGF-ß1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity. Immunity. 2020 12 15; 53(6):1202-1214.e6. View Abstract
  16. Omeprazole inhibits IgE-mediated mast cell activation and allergic inflammation induced by ingested allergen in mice. J Allergy Clin Immunol. 2020 10; 146(4):884-893.e5. View Abstract
  17. The soluble isoform of human Fc?RI is an endogenous inhibitor of IgE-mediated mast cell responses. Allergy. 2019 02; 74(2):236-245. View Abstract
  18. Immunoglobulin E blockade during food allergen ingestion enhances the induction of inhibitory immunoglobulin G antibodies. Ann Allergy Asthma Immunol. 2019 02; 122(2):213-215. View Abstract
  19. Tissue-Specific Expression of the Low-Affinity IgG Receptor, Fc?RIIb, on Human Mast Cells. Front Immunol. 2018; 9:1244. View Abstract
  20. Importance of basophils in eosinophilic asthma: the murine counterpart. J Biol Regul Homeost Agents. 2018 Mar-Apr; 32(2):335-339. View Abstract
  21. IgE promotes type 2 innate lymphoid cells in murine food allergy. Clin Exp Allergy. 2018 03; 48(3):288-296. View Abstract
  22. Food allergy. Nat Rev Dis Primers. 2018 01 04; 4:17098. View Abstract
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  24. Allergen-specific IgG antibody signaling through Fc?RIIb promotes food tolerance. J Allergy Clin Immunol. 2018 01; 141(1):189-201.e3. View Abstract
  25. A humanized mouse model of anaphylactic peanut allergy. J Allergy Clin Immunol. 2017 01; 139(1):314-322.e9. View Abstract
  26. Fifty years later: Emerging functions of IgE antibodies in host defense, immune regulation, and allergic diseases. J Allergy Clin Immunol. 2016 06; 137(6):1631-1645. View Abstract
  27. IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function. J Allergy Clin Immunol. 2016 09; 138(3):801-811.e9. View Abstract
  28. IgE receptor signaling in food allergy pathogenesis. Curr Opin Immunol. 2015 Oct; 36:109-14. View Abstract
  29. IgE and Mast Cells: The Endogenous Adjuvant. Adv Immunol. 2015; 127:203-56. View Abstract
  30. Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy. Immunity. 2015 Mar 17; 42(3):512-23. View Abstract
  31. Polyclonal IgE Induces Mast Cell Survival and Cytokine Production. Allergol Int. 2009; 58(3):411-419. View Abstract
  32. Anti-IgE therapy: clinical utility and mechanistic insights. Curr Top Microbiol Immunol. 2015; 388:39-61. View Abstract
  33. Oral immunotherapy induces IgG antibodies that act through Fc?RIIb to suppress IgE-mediated hypersensitivity. J Allergy Clin Immunol. 2014 Dec; 134(6):1310-1317.e6. View Abstract
  34. 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):141-51. View Abstract
  35. Food allergy: Insights into etiology, prevention, and treatment provided by murine models. J Allergy Clin Immunol. 2014 Feb; 133(2):309-17. View Abstract
  36. Basophils are rapidly mobilized following initial aeroallergen encounter in naïve mice and provide a priming source of IL-4 in adaptive immune responses. J Biol Regul Homeost Agents. 2014 Jan-Mar; 28(1):91-103. View Abstract
  37. IL-10 suppresses IL-17-mediated dermal inflammation and reduces the systemic burden of Vaccinia virus in a mouse model of eczema vaccinatum. Clin Immunol. 2014 Feb; 150(2):153-60. View Abstract
  38. An IgE receptor mimetic peptide (PepE) protects mice from IgE mediated anaphylaxis. Mol Biosyst. 2013 Nov; 9(11):2853-9. View Abstract
  39. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity. 2013 Nov 14; 39(5):963-75. View Abstract
  40. Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis. J Allergy Clin Immunol. 2013 Feb; 131(2):451-60.e1-6. View Abstract
  41. A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis. J Allergy Clin Immunol. 2013 Jan; 131(1):201-12. View Abstract
  42. Direct effects of IL-4 on mast cells drive their intestinal expansion and increase susceptibility to anaphylaxis in a murine model of food allergy. Mucosal Immunol. 2013 Jul; 6(4):740-50. View Abstract
  43. IL-21 is the primary common ? chain-binding cytokine required for human B-cell differentiation in vivo. Blood. 2011 Dec 22; 118(26):6824-35. View Abstract
  44. Beyond immediate hypersensitivity: evolving roles for IgE antibodies in immune homeostasis and allergic diseases. Immunol Rev. 2011 Jul; 242(1):128-43. View Abstract
  45. Distinct immune effector pathways contribute to the full expression of peanut-induced anaphylactic reactions in mice. J Allergy Clin Immunol. 2011 Jun; 127(6):1552-61.e1. View Abstract
  46. High-affinity IgE receptors on dendritic cells exacerbate Th2-dependent inflammation. J Immunol. 2011 Jul 01; 187(1):164-71. View Abstract
  47. Mast cells and tumour necrosis factor alpha (TNF-a): partners in crime in asthma pathogenesis. Clin Immunol. 2011 Jul; 140(1):1-2. View Abstract
  48. IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling. J Allergy Clin Immunol. 2011 Mar; 127(3):795-805.e1-6. View Abstract
  49. Immune response to varicella vaccine in children with atopic dermatitis compared with nonatopic controls. J Allergy Clin Immunol. 2010 Dec; 126(6):1306-7.e2. View Abstract
  50. Anti-IgE in the treatment of allergic disorders in pediatrics. Curr Opin Pediatr. 2010 Dec; 22(6):758-64. View Abstract
  51. Skin inflammation arising from cutaneous regulatory T cell deficiency leads to impaired viral immune responses. J Immunol. 2010 Jul 15; 185(2):1295-302. View Abstract
  52. In vivo regulation of the allergic response by the IL-4 receptor alpha chain immunoreceptor tyrosine-based inhibitory motif. J Allergy Clin Immunol. 2010 May; 125(5):1128-1136.e8. View Abstract
  53. Adaptive immunity. J Allergy Clin Immunol. 2010 Feb; 125(2 Suppl 2):S33-40. View Abstract
  54. Exaggerated IL-17 response to epicutaneous sensitization mediates airway inflammation in the absence of IL-4 and IL-13. J Allergy Clin Immunol. 2009 Oct; 124(4):761-70.e1. View Abstract
  55. Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma. J Exp Med. 2009 Sep 28; 206(10):2191-204. View Abstract
  56. Vaccinia virus inoculation in sites of allergic skin inflammation elicits a vigorous cutaneous IL-17 response. Proc Natl Acad Sci U S A. 2009 Sep 01; 106(35):14954-9. View Abstract
  57. Polyclonal IgE induces mast cell survival and cytokine production. Allergol Int. 2009 Sep; 58(3):411-9. View Abstract
  58. Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiation. Immunity. 2009 Apr 17; 30(4):533-43. View Abstract
  59. Toll-like receptor 2 is important for the T(H)1 response to cutaneous sensitization. J Allergy Clin Immunol. 2009 Apr; 123(4):875-82.e1. View Abstract
  60. Novel presentation of Omenn syndrome in association with aniridia. J Allergy Clin Immunol. 2009 Apr; 123(4):966-9. View Abstract
  61. IgE influences the number and function of mature mast cells, but not progenitor recruitment in allergic pulmonary inflammation. J Immunol. 2009 Feb 15; 182(4):2416-24. View Abstract
  62. IL-21R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice. J Clin Invest. 2009 Jan; 119(1):47-60. View Abstract
  63. Immunoglobulin E antibodies enhance pulmonary inflammation induced by inhalation of a chemical hapten. Clin Exp Allergy. 2009 Mar; 39(3):417-25. View Abstract
  64. Polyclonal and specific antibodies mediate protective immunity against enteric helminth infection. Cell Host Microbe. 2008 Oct 16; 4(4):362-73. View Abstract
  65. Mouse mast cell tryptase mMCP-6 is a critical link between adaptive and innate immunity in the chronic phase of Trichinella spiralis infection. J Immunol. 2008 Apr 01; 180(7):4885-91. View Abstract
  66. TNF receptor-associated factor 1 expressed in resident lung cells is required for the development of allergic lung inflammation. J Immunol. 2008 Feb 01; 180(3):1878-85. View Abstract
  67. Impaired immune response to vaccinia virus inoculated at the site of cutaneous allergic inflammation. J Allergy Clin Immunol. 2007 Dec; 120(6):1382-8. View Abstract
  68. Skin inflammation in RelB(-/-) mice leads to defective immunity and impaired clearance of vaccinia virus. J Allergy Clin Immunol. 2007 Mar; 119(3):671-9. View Abstract
  69. The H1 histamine receptor regulates allergic lung responses. J Clin Invest. 2006 Jun; 116(6):1624-32. View Abstract
  70. The complement component C3 plays a critical role in both Th1 and Th2 responses to antigen. J Allergy Clin Immunol. 2006 Jun; 117(6):1455-61. View Abstract
  71. TRAF1 regulates Th2 differentiation, allergic inflammation and nuclear localization of the Th2 transcription factor, NIP45. Int Immunol. 2006 Jan; 18(1):101-11. View Abstract
  72. COX-2 inhibition enhances the TH2 immune response to epicutaneous sensitization. J Allergy Clin Immunol. 2005 Aug; 116(2):390-6. View Abstract
  73. Antigen-independent effects of immunoglobulin E. Curr Allergy Asthma Rep. 2005 May; 5(3):186-90. View Abstract
  74. Cytotoxic T-cells specific for natural IgE peptides downregulate IgE production. Cell Immunol. 2005 Jan; 233(1):11-22. View Abstract
  75. Immune sensitization in the skin is enhanced by antigen-independent effects of IgE on mast cells. Novartis Found Symp. 2005; 271:15-24; discussion 24-38, 95-9. View Abstract
  76. The anaphylatoxin C3a downregulates the Th2 response to epicutaneously introduced antigen. J Clin Invest. 2004 Aug; 114(3):399-407. View Abstract
  77. Immune sensitization in the skin is enhanced by antigen-independent effects of IgE. Immunity. 2004 Apr; 20(4):381-92. View Abstract
  78. Effect of environmental intervention on mouse allergen levels in homes of inner-city Boston children with asthma. Ann Allergy Asthma Immunol. 2004 Apr; 92(4):420-5. View Abstract
  79. IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis. J Immunol. 2004 Jan 15; 172(2):1139-45. View Abstract
  80. Epicutaneous sensitization with superantigen induces allergic skin inflammation. J Allergy Clin Immunol. 2003 Nov; 112(5):981-7. View Abstract
  81. Targeted inactivation of the IL-4 receptor alpha chain I4R motif promotes allergic airway inflammation. J Exp Med. 2003 Oct 20; 198(8):1189-200. View Abstract
  82. IL-10 is critical for Th2 responses in a murine model of allergic dermatitis. J Clin Invest. 2003 Oct; 112(7):1058-66. View Abstract
  83. Management of an anaphylactoid reaction to methotrexate with a stepwise graded challenge. Pediatr Allergy Immunol. 2003 Oct; 14(5):409-11. View Abstract
  84. Desloratadine inhibits allergen-induced airway inflammation and bronchial hyperresponsiveness and alters T-cell responses in murine models of asthma. J Allergy Clin Immunol. 2003 Jul; 112(1):149-58. View Abstract
  85. CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. J Clin Invest. 2002 Mar; 109(5):621-8. View Abstract
  86. Giant cell myocarditis in a 12-year-old girl with common variable immunodeficiency. Mayo Clin Proc. 2002 Jan; 77(1):92-6. View Abstract
  87. Mast cells regulate IFN-gamma expression in the skin and circulating IgE levels in allergen-induced skin inflammation. J Allergy Clin Immunol. 2002 Jan; 109(1):106-13. View Abstract
  88. Alterations of the X-linked lymphoproliferative disease gene SH2D1A in common variable immunodeficiency syndrome. Blood. 2001 Sep 01; 98(5):1321-5. View Abstract
  89. IgE regulation and roles in asthma pathogenesis. J Allergy Clin Immunol. 2001 Mar; 107(3):429-40. View Abstract
  90. Resolution of bronchial hyperresponsiveness and pulmonary inflammation is associated with IL-3 and tissue leukocyte apoptosis. J Immunol. 2001 Feb 01; 166(3):2033-40. View Abstract
  91. An obligate role for T-cell receptor alphabeta+ T cells but not T-cell receptor gammadelta+ T cells, B cells, or CD40/CD40L interactions in a mouse model of atopic dermatitis. J Allergy Clin Immunol. 2001 Feb; 107(2):359-66. View Abstract
  92. Regulation of the IgE isotype switch: new insights on cytokine signals and the functions of epsilon germline transcripts. Curr Opin Immunol. 2000 Dec; 12(6):618-23. View Abstract
  93. CD40L, but not CD40, is required for allergen-induced bronchial hyperresponsiveness in mice. Am J Respir Cell Mol Biol. 2000 Nov; 23(5):646-51. View Abstract
  94. IgE in asthma and atopy: cellular and molecular connections. J Clin Invest. 1999 Oct; 104(7):829-35. View Abstract
  95. SLP-76 deficiency impairs signaling via the high-affinity IgE receptor in mast cells. J Clin Invest. 1999 Jun; 103(12):1737-43. View Abstract
  96. Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. J Clin Invest. 1999 Apr; 103(8):1103-11. View Abstract
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  99. Molecular and biological characterization of the murine leukotriene B4 receptor expressed on eosinophils. J Exp Med. 1998 Sep 21; 188(6):1063-74. View Abstract
  100. The expression of murine B cell CD23, in vivo, is regulated by its ligand, IgE. Int Immunol. 1998 Sep; 10(9):1377-84. View Abstract
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