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

Schröder, Paul C. and Casaca, Vera I. and Illi, Sabina and Schieck, Maximilian and Michel, Sven and Böck, Andreas and Roduit, Caroline and Frei, Remo and Lluis, Anna and Genuneit, Jon and Pfefferle, Petra and Roponen, Marjut and Weber, Juliane and Braun-Fahrländer, Charlotte and Riedler, Josef and Lauener, Roger and Vuitton, Dominique Angèle and Dalphin, Jean-Charles and Pekkanen, Juha and von Mutius, Erika and Kabesch, Michael and Schaub, Bianca and Pasture Study group, . (2016) IL-33 polymorphisms are associated with increased risk of hay fever and reduced regulatory T cells in a birth cohort. Pediatric allergy and immunology, 27 (7). pp. 687-695.

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Official URL: http://edoc.unibas.ch/44658/

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Abstract

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.; 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.; 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.; 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Environmental Exposures and Health > Physical Hazards and Health (Röösli)
UniBasel Contributors:Braun-Fahrländer, Charlotte
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Blackwell
ISSN:0905-6157
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:06 Dec 2016 08:25
Deposited On:06 Dec 2016 08:25

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