A switch in regulatory T cells through farm exposure during immune maturation in childhood.
Allergy
; 72(4): 604-615, 2017 Apr.
Article
en En
| MEDLINE
| ID: mdl-27732759
ABSTRACT
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+ CD25high FOXP3upper20% ). 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Subgrupos de Linfocitos T
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Linfocitos T Reguladores
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Exposición a Riesgos Ambientales
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Granjas
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Inmunidad
Tipo de estudio:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Límite:
Animals
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
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Pregnancy
Idioma:
En
Revista:
Allergy
Año:
2017
Tipo del documento:
Article
País de afiliación:
Alemania