Science and Research

A switch in regulatory T cells through farm exposure during immune maturation in childhood

BACKGROUND: Farm exposure protects against development of allergies early in life. At 4.5 years, protection against asthma by farm-milk exposure was partially mediated by regulatory T cells (Tregs). The aim of this study was to investigate the critical time window of the 'asthma-protective' farm effect via Tregs during childhood immune maturation. METHODS: Tregs were assessed longitudinally at 4.5 and 6 years in 111 children (56 farm and 55 reference children) from the PASTURE/EFRAIM birth cohort (flow cytometry). Peripheral blood mononuclear cells were cultured unstimulated (U), with phorbol 12-myristate 13-acetate/ionomycin (PI) or lipopolysaccharide (LPS), and stained for Tregs (CD4(+) CD25(high) FOXP3(upper20%) ). mRNA expression of Treg/Th1/Th2/Th17-associated cell markers was measured ex vivo. Suppressive capacity of Tregs on effector cells and cytokines was assessed. Detailed questionnaires assessing farm exposures and clinical phenotypes from birth until age 6 years were answered by the parents. RESULTS: Treg percentage before and after stimulation and FOXP3mRNA expression ex vivo decreased from age 4.5 to 6 years (P(U,LPS) < 0.001; P(PI) = 0.051; P(FOXP3) < 0.001). High vs low farm-milk and animal-stable exposure was associated with decreased LPS-stimulated Treg percentage at age 6 years (P(LPS) = 0.045). Elevated LPS-stimulated-Treg percentage at age 6 was associated with increased risk of asthma (aOR = 11.29, CI: 0.96-132.28, P = 0.053). Tregs from asthmatics vs nonasthmatics suppressed IFN-gamma (P = 0.015) and IL-9 (P = 0.023) less efficiently. mRNA expression of Th1/Th2/Th17-associated cell markers decreased between 4.5 and 6 years (P < 0.001). CONCLUSIONS: Tregs at the age of 6 years were decreased with farm exposure and increased within asthmatics, opposite to age 4.5 years. This immunological switch defines a critical 'time window' for Treg-mediated asthma protection via environmental exposure before age 6 years.
  • Schroder, P. C.
  • Illi, S.
  • Casaca, V. I.
  • Lluis, A.
  • Bock, A.
  • Roduit, C.
  • Depner, M.
  • Frei, R.
  • Genuneit, J.
  • Pfefferle, P. I.
  • Roponen, M.
  • Weber, J.
  • Braun-Fahrlander, C.
  • Riedler, J.
  • Dalphin, J. C.
  • Pekkanen, J.
  • Lauener, R.
  • von Mutius, E.
  • Schaub, B.
  • Pasture study group

Keywords

  • Age Factors
  • Allergens/immunology
  • Animals
  • Asthma/epidemiology/etiology
  • Biomarkers
  • Child
  • Child, Preschool
  • Cytokines/metabolism
  • *Environmental Exposure
  • *Farms
  • Female
  • Follow-Up Studies
  • Gene Expression
  • Humans
  • *Immunity
  • Immunoglobulin E/immunology
  • Infant
  • Infant, Newborn
  • Lymphocyte Count
  • Male
  • Phenotype
  • Population Surveillance
  • Pregnancy
  • RNA, Messenger/genetics
  • Surveys and Questionnaires
  • T-Lymphocyte Subsets/*immunology/metabolism
  • T-Lymphocytes, Regulatory/*immunology/metabolism
  • animal-stable
  • asthma
  • farming
  • milk
  • regulatory T cells (Tregs)
Publication details
DOI: 10.1111/all.13069
Journal: Allergy
Pages: 604-615 
Number: 4
Work Type: Original
Location: CPC-M, UGMLC
Disease Area: AA
Partner / Member: LMU, UMR
Access-Number: 27732759
See publication on PubMed

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