IL-33 polymorphisms are associated with increased risk of hay fever and reduced regulatory T cells in a birth cohort

Autor: Jean-Charles Dalphin, Andreas Böck, Jon Genuneit, Sabina Illi, Charlotte Braun-Fahrländer, Sven Michel, Josef Riedler, Dominique A. Vuitton, Erika von Mutius, Marjut Roponen, Juha Pekkanen, Maximilian Schieck, P. C. Schröder, Bianca Schaub, Juliane Weber, Remo Frei, Roger Lauener, Vera Isabel Casaca, Caroline Roduit, Petra Ina Pfefferle, Anna Lluis, Michael Kabesch
Přispěvatelé: Université de Montpellier (UM), Universität Duisburg-Essen [Essen], Children's Hospital, University hospital of Zurich [Zurich], Christine Kühne – Centre for Allergy Research and Education (CK-CARE), Institute of Epidemiology, Universität Ulm - Ulm University [Ulm, Allemagne], Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB / CAS), Czech Academy of Sciences [Prague] (CAS), University of Basel (Unibas), Swiss Tropical and Public Health Institute [Basel], Kardinal Schwarzenberg’sches Krankenhaus, 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), University of Munich, University of Zurich, Schaub, Bianca, Université de Montpellier ( UM ), Christine Kühne – Centre for Allergy Research and Education ( CK-CARE ), Universität Ulm, Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, University of Basel ( Unibas ), 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 )
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Risk
Allergy
Genotype
Immunology
IL1RL1
610 Medicine & health
Polymorphism
Single Nucleotide
T-Lymphocytes
Regulatory
Allergic inflammation
[ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology
environment/Health
Cohort Studies
03 medical and health sciences
Gene Frequency
10183 Swiss Institute of Allergy and Asthma Research
Germany
Immunology and Allergy
Medicine
Humans
Genetic Predisposition to Disease
IL-2 receptor
2735 Pediatrics
Perinatology and Child Health
Allele
Child
Cells
Cultured
2. Zero hunger
[SDV.EE.SANT]Life Sciences [q-bio]/Ecology
environment/Health
2403 Immunology
business.industry
FOXP3
Rhinitis
Allergic
Seasonal
Forkhead Transcription Factors
medicine.disease
Interleukin-33
3. Good health
Minor allele frequency
030104 developmental biology
Suppressor of Cytokine Signaling 3 Protein
10036 Medical Clinic
Child
Preschool
Pediatrics
Perinatology and Child Health
2723 Immunology and Allergy
Hay fever
Female
business
Zdroj: Pediatric Allergy and Immunology
Pediatric Allergy and Immunology, Wiley, 2016
ISSN: 0905-6157
1399-3038
Popis: Background: IL-33 polymorphisms influence the susceptibility to asthma. IL-33 indirectly induces Th2-immune responses via dendritic cell activation, being important for development of atopic diseases. Furthermore, IL-33 upregulates regulatory T cells (Tregs), which are critical for healthy immune homeostasis. This study investigates associations between IL-33 polymorphisms during the development of childhood atopic diseases and underlying mechanisms including immune regulation of Tregs. Methods: Genotyping of IL-33-polymorphisms (rs928413, rs1342326) was performed by MALDI-TOF-MS in 880 of 1133 PASTURE/EFRAIM children. In 4.5-year-old German PASTURE/EFRAIM children (n = 99), CD4(+) CD25(high)FOXP3(+) Tregs were assessed by flow cytometry following 24-h incubation of PBMCs with PMA/ionomycin, LPS or without stimuli (U). SOCS3, IL1RL1, TLR4 mRNA expression and sST2 protein levels ex vivo were measured in PASTURE/EFRAIM children by real-time PCR or ELISA, respectively. Health outcomes (hay fever, asthma) were assessed by questionnaires at the age of 6 years. Results: rs928413 and rs1342326 were positively associated with hay fever (OR = 1.77, 95% CI = 1.02-3.08;OR = 1.79, 95% CI = 1.04-3.11) and CD4(+) CD25(high)FOXP3(+) Tregs (%) decreased in minor allele homozygotes/heterozygotes compared to major allele homozygotes (p(U) = 0.004;p(LPS) = 0.005;p(U) = 0.001;p(LPS) = 0.012). SOCS3 mRNA expression increased in minor allele homozygotes and heterozygotes compared with major allele homozygotes for both IL-33-polymorphisms (p (rs928413) = 0.032, p(rs1342326) = 0.019) and negatively correlated to Tregs. Conclusions: IL-33-polymorphisms rs928413 and rs1342326 may account for an increased risk of hay fever with the age of 6 years. Lower Tregs and increased SOCS3 in combined heterozygotes and minor allele homozygotes may be relevant for hay fever development, pointing towards dysbalanced immune regulation and insufficient control of allergic inflammation.
Databáze: OpenAIRE
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