Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood

Autor: Roger Lauener, Vera Isabel Casaca, Caroline Roduit, R. Frei, Juha Pekkanen, Anna Lluis, Josef Riedler, Jean-Charles Dalphin, Harald Renz, Marie-Laure Dalphin, S. Remes, Michael Kabesch, Maija-Riitta Hirvonen, Béatrice Gaugler, Dominique A. Vuitton, Jon Genuneit, Jörg Tost, Juliane Weber, Georg Loss, Diana Raedler, Marjut Roponen, Philippe Saas, Vincent Kaulek, Gisela Büchele, Anne Hyvärinen, Charlotte Braun-Fahrländer, Jing Liu, Martin Depner, Bianca Schaub, Pekka Tiittanen, Erika von Mutius, Gert Doekes, S. Bitter, Petra Ina Pfefferle, Sven Michel, Anne M. Karvonen
Přispěvatelé: Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Xi'an Jiaotong University ( Xjtu ), Institute of Epidemiology, Universität Ulm, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Asthma and Allergy Department, University Children's Hospital-Ludwig Maximilians University, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Xi'an Jiaotong University (Xjtu), Universität Ulm - Ulm University [Ulm, Allemagne], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Laboratoire Chrono-environnement (UMR 6249) (LCE), University Children's Hospital-Ludwig-Maximilians University [Munich] (LMU)
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Hypersensitivity
Immediate
Male
Allergy
MESH: Asthma
MESH: CD4 Lymphocyte Count
MESH : Prospective Studies
MESH : Child
Preschool
Immunoglobulin E
MESH : Agriculture
MESH : Hypersensitivity
Immediate
T-Lymphocytes
Regulatory
Atopy
MESH : T-Lymphocytes
Regulatory
MESH: Pregnancy
MESH: DNA Methylation
Pregnancy
Immunology and Allergy
MESH: Animals
MESH : Female
IL-2 receptor
Prospective Studies
Sensitization
2. Zero hunger
biology
MESH: Immunoglobulin E
FOXP3
Agriculture
Forkhead Transcription Factors
hemic and immune systems
MESH : Infant
MESH: Infant
3. Good health
Europe
MESH : Forkhead Transcription Factors
medicine.anatomical_structure
Milk
Child
Preschool
Female
MESH: Hypersensitivity
Immediate
MESH: Agriculture
Regulatory T cell
MESH : Male
Immunology
MESH : Europe
chemical and pharmacologic phenomena
MESH : Asthma
MESH : Immunoglobulin E
[ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology
environment/Health
MESH: Forkhead Transcription Factors
medicine
MESH : CD4 Lymphocyte Count
Animals
Humans
Asthma
[SDV.EE.SANT]Life Sciences [q-bio]/Ecology
environment/Health
MESH: Humans
business.industry
MESH: T-Lymphocytes
Regulatory
MESH: Child
Preschool
MESH : Humans
Infant
DNA Methylation
medicine.disease
MESH: Male
MESH: Prospective Studies
CD4 Lymphocyte Count
MESH: Milk
MESH : Pregnancy
MESH : Milk
biology.protein
MESH: Europe
MESH : Animals
business
MESH: Female
MESH : DNA Methylation
Zdroj: Journal of Allergy and Clinical Immunology
Journal of Allergy and Clinical Immunology, Elsevier, 2014, 133 (2), pp.551-9. 〈10.1016/j.jaci.2013.06.034〉
Journal of Allergy and Clinical Immunology, Elsevier, 2014, 133 (2), pp.551-9. ⟨10.1016/j.jaci.2013.06.034⟩
Journal of Allergy and Clinical Immunology, 2014, 133 (2), pp.551-9. ⟨10.1016/j.jaci.2013.06.034⟩
ISSN: 0091-6749
DOI: 10.1016/j.jaci.2013.06.034〉
Popis: International audience; BACKGROUND: European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. OBJECTIVE: We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. METHODS: From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4(+)CD25(+) forkhead box protein 3 (FOXP3)(+) (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. RESULTS: Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4(+)CD25(+), FOXP3(+) T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. CONCLUSIONS: Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.
Databáze: OpenAIRE
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