title: The farming environment protects mice from allergen-induced skin contact hypersensitivity.
abstract: BACKGROUND
  Being born and raised in a farm provides a long-lasting protection for allergies. The microbial environment provided by farm animals is crucial to induce this protective effect, although underlying immune mechanisms remain elusive.
  
  
  OBJECTIVE
  To establish a mouse model of global exposure to the farming environment and to study immunologic changes linked to protection of allergy.
  
  
  METHODS
  Mice colonies were bred in parallel in a farm cowshed and the university animal facility (AF). Mice from both locations were subjected to a skin contact allergy model. Peripheral blood cells and cell cytokine production were assessed in both populations. In addition, the gut microbiome at various ages was characterized.
  
  
  RESULTS
  Mice born in the farm were less prone to develop allergy than mice bred in the AF. Mice transfers between the AF and the farm showed a better protection when mice were moved to the farm early in life. As compared to AF-bred mice, farm mice displayed early immune activation with higher CD4+T cell population, in particular CD4+CD25+FoxP3-(activated cells). The cytokine profile of mice from the farm was skewed towards an IL-17 and IL-22 secreting cell profile accompanied by increased IL-10 secretion. These differences were mostly seen within a specific age window between birth and 8 weeks of age. Microbiome analysis showed differences between 4 and 20 weeks old mice and between farm and AF mice with an increased number of Murine mastadenovirus B in young farm mice exclusively.
  
  
  CONCLUSIONS
  The farming environment provides a strong, allergy protective IL-22 stimulus and generates activated CD4+ T cells. Exposure to the farm environment early in their life may also provide a better protection for contact skin allergy. Whether a viral trigger might decisively influence protection for allergies remains to be determined.
authors.affiliation: Inflammation and Allergy Research Group, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
authors.forename: C P
authors.initials: CP
authors.lastname: Frossard
authors.affiliation: Genomic Research Laboratory, Division of Infectious Diseases, Departments of Pediatrics, Anesthesiology, and Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.|Division of Laboratory Medicine, Departments of Pediatrics, Anesthesiology, and Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Lazarevic
authors.affiliation: Genomic Research Laboratory, Division of Infectious Diseases, Departments of Pediatrics, Anesthesiology, and Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.|Division of Laboratory Medicine, Departments of Pediatrics, Anesthesiology, and Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Gaïa
authors.affiliation: Genomic Research Laboratory, Division of Infectious Diseases, Departments of Pediatrics, Anesthesiology, and Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.|Division of Laboratory Medicine, Departments of Pediatrics, Anesthesiology, and Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Leo
authors.affiliation: Division of Anesthesiology Investigation, Departments of Pediatrics, Anesthesiology, and Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Doras
authors.affiliation: Division of Anesthesiology Investigation, Departments of Pediatrics, Anesthesiology, and Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: Habre
authors.affiliation: Genomic Research Laboratory, Division of Infectious Diseases, Departments of Pediatrics, Anesthesiology, and Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.|Division of Laboratory Medicine, Departments of Pediatrics, Anesthesiology, and Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Schrenzel
authors.affiliation: Inflammation and Allergy Research Group, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.|Hans Wilsdorf Laboratory, Departments of Pediatrics, Anesthesiology, and Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Burger
authors.affiliation: Inflammation and Allergy Research Group, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
authors.forename: P A
authors.identifier: http://orcid.org/0000-0003-1738-1826
authors.initials: PA
authors.lastname: Eigenmann
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000382:microbiology; D000072480:Farms; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000485:Allergens
keywords: Mastadenoviruses; T cell tolerance; allergy; farming environment; gut microbiome