Format

Send to

Choose Destination
Pediatr Allergy Immunol. 2016 Nov;27(7):687-695. doi: 10.1111/pai.12597. Epub 2016 Jul 12.

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

Author information

1
LMU Munich, University Children's Hospital, Munich, Germany.
2
Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.
3
Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.
4
Children's Hospital, and Christine Kühne-Center for Allergy Research and Education, University of Zurich, Zurich, Switzerland.
5
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
6
Christine Kühne-Center for Allergy research and Education, Hochgebirgsklinik Davos-Wolfgang, Davos, Switzerland.
7
National Jewish Health, Denver, CO, USA.
8
Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
9
Department of Clinical Chemistry and Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.
10
Living Environment and Health Unit, National Institute for Health and Welfare, Kuopio, Finland.
11
Swiss Tropical and Public Health Institute, Basel, Switzerland.
12
University of Basel, Basel, Switzerland.
13
Children's Hospital Schwarzach, Schwarzach, Austria.
14
Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland.
15
University Hospital of Besançon, the Research Unit Health and Rural Environment, University of Franche-Comté, Besançon, France.
16
Department of Public health, University of Helsinki, Helsinki, Finland.
17
LMU Munich, University Children's Hospital, Munich, Germany. Bianca.Schaub@med.uni-muenchen.de.

Abstract

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+ CD25high 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+ CD25high 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.

KEYWORDS:

IL-33 ; Tregs; childhood; hay fever; polymorphisms

PMID:
27171815
DOI:
10.1111/pai.12597
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center