title: Allergen-induced IgE-dependent gut inflammation in a human PBMC-engrafted murine model of allergy.
abstract: BACKGROUND
  Humanized murine models comprise a new tool to analyze novel therapeutic strategies for allergic diseases of the intestine.
  
  
  OBJECTIVE
  In this study we developed a human PBMC-engrafted murine model of allergen-driven gut inflammation and analyzed the underlying immunologic mechanisms.
  
  
  METHODS
  Nonobese diabetic (NOD)-scid-γc(-/-) mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or not. Three weeks later, mice were challenged with the allergen orally or rectally, and gut inflammation was monitored with a high-resolution video miniendoscopic system, as well as histologically.
  
  
  RESULTS
  Using the aeroallergens birch or grass pollen as model allergens and, for some donors, also hazelnut allergen, we show that allergen-specific human IgE in murine sera and allergen-specific proliferation and cytokine production of human CD4(+) T cells recovered from spleens after 3 weeks could only be measured in mice treated with PBMCs plus allergen. Importantly, these mice had the highest endoscopic scores evaluating translucent structure, granularity, fibrin, vascularity, and stool after oral or rectal allergen challenge and a strong histologic inflammation of the colon. Analyzing the underlying mechanisms, we demonstrate that allergen-associated colitis was dependent on IgE, human IgE receptor-expressing effector cells, and the mediators histamine and platelet-activating factor.
  
  
  CONCLUSIONS
  These results demonstrate that allergic gut inflammation can be induced in human PBMC-engrafted mice, allowing the investigation of pathophysiologic mechanisms of allergic diseases of the intestine and evaluation of therapeutic interventions.
authors.affiliation: University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Benno
authors.initials: B
authors.lastname: Weigmann
authors.forename: Nadja
authors.initials: N
authors.lastname: Schughart
authors.forename: Christian
authors.initials: C
authors.lastname: Wiebe
authors.forename: Stephan
authors.initials: S
authors.lastname: Sudowe
authors.forename: Hans A
authors.initials: HA
authors.lastname: Lehr
authors.forename: Helmut
authors.initials: H
authors.lastname: Jonuleit
authors.forename: Lothar
authors.initials: L
authors.lastname: Vogel
authors.forename: Christoph
authors.initials: C
authors.lastname: Becker
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
authors.forename: Stephan
authors.initials: S
authors.lastname: Grabbe
authors.forename: Joachim
authors.initials: J
authors.lastname: Saloga
authors.forename: Iris
authors.initials: I
authors.lastname: Bellinghausen
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005756:Gastritis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006633:Histamine Antagonists / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011058:Pollen / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D017455:Receptors, IgE / Q000378:metabolism; D013154:Spleen / Q000276:immunology
chemical_list: D000485:Allergens; D016207:Cytokines; D006633:Histamine Antagonists; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D017455:Receptors, IgE; C039351:platelet activating factor receptor; D007073:Immunoglobulin E