Clinical & Experimental Allergy

Association between suppressors of cytokine signalling, T-helper type 1/T-helper type 2 balance and allergic sensitization in children

Authors

  • C. Daegelmann,

    1. Department of Environmental Immunology,
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  • G. Herberth,

    1. Department of Environmental Immunology,
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  • S. Röder,

    1. Department of Human Exposure Research and Epidemiology, UFZ – Helmholtz Centre for Environmental Research, Leipzig, Germany,
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  • O. Herbarth,

    1. Department of Human Exposure Research and Epidemiology, UFZ – Helmholtz Centre for Environmental Research, Leipzig, Germany,
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  • T. Giese,

    1. Institute for Immunology, University Heidelberg, Heidelberg, Germany,
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  • U. Krämer,

    1. Epidemiology, IUF-Institute for Environmental Medicine Research, Duesseldorf, Germany,
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  • H. Behrendt,

    1. Division Environmental Dermatology and Allergy GSF/TUM, ZAUM – Centre for Allergy and Environment, Technical University Munich, Munich, Germany,
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  • M. Borte,

    1. Children's Hospital, Municipal Hospital ‘St Georg’, Leipzig, Germany,
    2. Department of Pediatrics, University of Leipzig, Leipzig, Germany,
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  • J. Heinrich,

    1. GSF-National Research Centre for Environment and Health, Institute of Epidemiology, Neuherberg, Germany
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  • F. Emmrich,

    1. Institute of Clinical Immunology and Transfusion Medicine, University of Leipzig, Leipzig, Germany
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  • I. Lehmann,

    1. Department of Environmental Immunology,
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  • for the LISAplus study group

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    • 1The LISAplus study group comprises following partners:
      GSF-National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg (Wichmann HE, Heinrich J, Bolte G, Belcredi P, Jacob B, Schoetzau A, Mosetter M, Schindler J, Höhnke A, Franke K, Laubereau B, Sausenthaler S, Thaqi A, Zirngibl A, Zutavern A); Department of Pediatrics, University of Leipzig (Borte M, Schulz R, Sierig G, Mirow K, Gebauer C, Schulze B); Department of Pediatrics, St Georg Hospital, Leipzig (Borte M, Diez U, Straub S); University of Leipzig, Institute of Clinical Immunology and Transfusion Medicine (Lehmann I, Sack U); Department of Pediatrics, Marien-Hospital, Wesel (von Berg A, Scholten C, Bollrath C, Groß I, Möllemann M); Bad Honnef (Schaaf B); Department of Human Exposure Research and Epidemiology, UFZ-Centre for Environmental Research Leipzig-Halle (Herbarth O, Bauer M, Franck U, Graebsch C, Mueller A, Rehwagen M, Richter M, Roeder S, Rolle-Kampczyk U, Schlink U, Albrecht S, Jorks A); Department of Environmental Immunology, UFZ- Centre for Environmental Research Leipzig-Halle (Lehmann I, Herberth G, Daegelmann C); Department of Pediatrics/Infectious diseases and Immunology, Ludwig Maximilians University, Munich (Weiss M, Albert M); Institute of Clinical Immunology, Friedrich-Schiller-University, Jena, (Fahlbusch B); Institute of Social, Occupational and Environmental Medicine (Bischof W, Koch A); IUF-Institut für Umweltmedizinische Forschung, Düsseldorf (Krämer U, Link E, Ranft U, Schins R, Sugiri D); Department of Pediatrics, Technical University, Munich (Bauer CP, Brockow I, Grübl A); Department of Dermatology, Technical University, Munich (Ring J, Grosch J, Darsow U, Weidinger S); Centre for Allergy and Environment, Technical University, Munich (Behrendt H, Kasche A, Buters J, Traidl-Hoffmann C); CCG Paediatric Immunology, Ludwig Maximilians University, Munich and GSF-National Research Center for Environment and Health (Krauss-Etschmann S); Institute of Social Medicine, University of Luebeck (Schäfer T).


Correspondence:
Irina Lehmann, Department of Environmental Immunology, UFZ – Helmholtz Centre for Environmental Research, Leipzig, Permoserstrasse 15, 04318 Leipzig, Germany.
E-mail: irina.lehmann@ufz.de

Summary

Background Suppressors of cytokine signalling (SOCS) family members have been shown to play an important role in the balance of cytokines that determine the onset of T-helper type 1 (Th1)- and Th2-mediated immune responses. In particular, for cytokine-induced Src-homology 2 protein (CIS), SOCS1, SOCS3 and SOCS5, a role in the regulation of T cell differentiation has been discussed. However, only few data exist so far in the human system.

Objectives The aim of the present study was to analyse the relationship between these suppressors and Th1/Th2 regulation as well as allergic sensitizations within a population-based study.

Methods Within the Lifestyle–Immune system–Allergy plus cohort study, mRNA was prepared from blood samples of 6-year-old children for the analysis of cytokines, transcription factors for T cell regulation and SOCS molecule expression by quantitative real-time polymerase chain reaction. In addition, total and specific IgE concentrations have been measured by the Pharmacia CAP System. A complete data set from 248 children was available.

Results Among the SOCS molecules investigated, only SOCS1 showed a strong positive correlation to allergic sensitizations. In addition, an up-regulated SOCS1 expression correlated with down-regulated T-box expressed in T cells (Tbet) and higher expression levels of GATA-binding protein 3 (GATA-3) and IL-4. No association between SOCS1 and forkhead box P3 (FOXP3) was observed. For SOCS3, SOCS5 and CIS, a contradictory picture was found. The expression of these SOCS molecules was positively correlated with Tbet and FOXP3 and (with the exception of CIS) negatively with IL-4.

Conclusions Our data suggest that SOCS3, SOCS5 and CIS, which correlate with an up-regulated Th1 and regulatory T cell activity, are without relevance for the allergic status. In contrast, SOCS1 might be involved in the development of a Th2-skewed immune response and subsequent allergic sensitizations.

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