title: A humanized mouse model of anaphylactic peanut allergy.
abstract: Food allergy is a growing health problem with very limited treatment options. Investigation of the immunologic pathways underlying allergic sensitization to foods in humans has been greatly constrained by the limited availability of intestinal tissue and gut-resident immune cells. Although mouse models have offered insights into pathways of food sensitization, differences between rodent and human immune physiology limit the extension of these findings to our understanding of human disease.
  
  
  
  We sought to develop a strategy for the generation of mice with humanized adaptive immune systems, complete with tissue engraftment by human mast cells that are competent to mount specific IgE-mediated responses and drive systemic anaphylaxis on ingestion challenge.
  
  
  
  Nonobese diabetic severe combined immunodeficient mice lacking the cytokine receptor common gamma chain (γc-/-) and carrying a human stem cell factor transgene were engrafted with human hematopoietic stem cells. The impact of peanut (PN) feeding and IgE neutralization on the development of immune responses, mast cell homeostasis, and anaphylactic food allergy was assessed in these animals.
  
  
  
  Humanized nonobese diabetic severe combined immunodeficient common gamma chain-deficient stem cell factor (huNSG) mice exhibited robust engraftment with functional human T and B lymphocytes and human mast cells were found in significant numbers in their tissues, including the intestinal mucosa. Following gavage feeding with PN, they mounted specific antibody responses, including PN-specific IgE. When enterally challenged with PN, they exhibited mast-cell-mediated systemic anaphylaxis, as indicated by hypothermia and increases in plasma tryptase levels. Anti-IgE (omalizumab) treatment ablated this anaphylactic response.
  
  
  
  huNSG mice provide a novel tool for studying food allergy and IgE-mediated anaphylaxis.
authors.affiliation: Department of Medicine, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass. Electronic address: oliver.burton@childrens.harvard.edu.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Burton
authors.affiliation: Department of Medicine, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Stranks
authors.affiliation: Department of Medicine, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass.
authors.forename: Jaciel M
authors.initials: JM
authors.lastname: Tamayo
authors.affiliation: Department of Medicine, Boston Children's Hospital, Boston, Mass.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Koleoglou
authors.affiliation: Division of Rheumatology, Allergy and Immunology and the Department of Internal Medicine, Virginia Commonwealth University, Richmond, Va.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schwartz
authors.affiliation: Department of Medicine, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Oettgen
mesh_terms: D000707:Anaphylaxis / Q000188:drug therapy / Q000276:immunology*; D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D008822:Mice, Transgenic; D000069444:Omalizumab / Q000627:therapeutic use; D021183:Peanut Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018926:Anti-Allergic Agents; D000069444:Omalizumab; D007073:Immunoglobulin E
keywords: IgE; anaphylaxis; humanized mice; mast cells; peanut allergy; tryptase