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

Autor: P C, Schröder, S, Illi, V I, Casaca, A, Lluis, A, Böck, C, Roduit, M, Depner, R, Frei, J, Genuneit, P I, Pfefferle, M, Roponen, J, Weber, C, Braun-Fahrländer, J, Riedler, J C, Dalphin, J, Pekkanen, R, Lauener, E, von Mutius, B, Schaub, Michael, Kabesch
Přispěvatelé: University of Zurich, Schaub, B
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Allergy
Lipopolysaccharide
Gene Expression
T-Lymphocytes
Regulatory
chemistry.chemical_compound
0302 clinical medicine
10183 Swiss Institute of Allergy and Asthma Research
Pregnancy
T-Lymphocyte Subsets
Surveys and Questionnaires
Immunology and Allergy
Child
Age Factors
FOXP3
Environmental exposure
Phenotype
Child
Preschool
Population Surveillance
2723 Immunology and Allergy
Cytokines
Female
Farms
Immunology
chemical and pharmacologic phenomena
610 Medicine & health
Biology
Peripheral blood mononuclear cell
03 medical and health sciences
Immune system
medicine
Animals
Humans
Lymphocyte Count
RNA
Messenger
Asthma
2403 Immunology
Immunity
Infant
Newborn
Infant
Environmental Exposure
Allergens
Immunoglobulin E
medicine.disease
030104 developmental biology
030228 respiratory system
chemistry
10036 Medical Clinic
Ex vivo
Biomarkers
Follow-Up Studies
Zdroj: Allergy. 72(4)
ISSN: 1398-9995
Popis: 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+CD25highFOXP3upper20%). 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-γ (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.
Databáze: OpenAIRE
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