title: Expression of genes related to anti-inflammatory pathways are modified among farmers' children.
abstract: BACKGROUND
  The hygiene hypothesis states that children exposed to higher loads of microbes such as farmers' children suffer less from allergies later in life. Several immunological mechanisms underpinning the hygiene hypothesis have been proposed such as a shift in T helper cell balance, T regulatory cell activity, or immune regulatory mechanisms induced by the innate immunity.
  
  
  OBJECTIVE
  To investigate whether the proposed immunological mechanisms for the hygiene hypotheses are found in farmers' children.
  
  
  METHODS
  We assessed gene expression levels of 64 essential markers of the innate and adaptive immunity by quantitative real-time PCR in white blood cells in 316 Swiss children of the PARSIFAL study to compare farmers' to non-farmers' expressions and to associate them to the prevalence of asthma and rhinoconjunctivitis, total and allergen-specific IgE in serum, and expression of Cε germ-line transcripts.
  
  
  RESULTS
  We found enhanced expression of genes of the innate immunity such as IRAK-4 and RIPK1 and enhanced expression of regulatory molecules such as IL-10, TGF-β, SOCS4, and IRAK-2 in farmers' children. Furthermore, farmers' children expressed less of the TH1 associated cytokine IFN-γ while TH2 associated transcription factor GATA3 was enhanced. No significant associations between the assessed immunological markers and allergic diseases or sensitization to allergens were observed.
  
  
  CONCLUSIONS
  Farmers' children express multiple increased innate immune response and immune regulatory molecules, which may contribute to the mechanisms of action of the hygiene hypothesis.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Zurich, Switzerland.
authors.forename: Remo
authors.initials: R
authors.lastname: Frei
authors.affiliation: Christine Kühne-Center for Allergy Research and Education, Zurich, Switzerland; Children's Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Roduit
authors.affiliation: Children's Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Bieli
authors.affiliation: Christine Kühne-Center for Allergy Research and Education, Zurich, Switzerland; Children's Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Loeliger
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Waser
authors.affiliation: Translational Immunology Unit, Department of Medicine Solna, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.affiliation: Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: van Hage
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Pershagen
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Doekes
authors.affiliation: Children's Hospital Schwarzach, Schwarzach, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Riedler
authors.affiliation: Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany.
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.affiliation: Children's Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Sennhauser
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Zurich, Switzerland.
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Braun-Fahrländer
authors.affiliation: Christine Kühne-Center for Allergy Research and Education, Zurich, Switzerland; Kantonsspital St.Gallen, St.Gallen, Switzerland.
authors.forename: Roger P
authors.initials: RP
authors.lastname: Lauener
mesh_terms: D000383:Agriculture; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003231:Conjunctivitis / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007073:Immunoglobulin E / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics*; D008297:Male; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D000078329:Workforce
chemical_list: D000485:Allergens; D016207:Cytokines; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors; D007073:Immunoglobulin E