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Regulatory T cells and immune regulation of allergic diseases: roles of IL-10 and TGF-β

Genes & Immunity volume 15, pages 511–520 (2014)Cite this article

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Abstract

The prevalence of allergic diseases has significantly increased in industrialized countries. Allergen-specific immunotherapy (AIT) remains as the only curative treatment. The knowledge about the mechanisms underlying healthy immune responses to allergens, the development of allergic reactions and restoration of appropriate immune responses to allergens has significantly improved over the last decades. It is now well-accepted that the generation and maintenance of functional allergen-specific regulatory T (Treg) cells and regulatory B (Breg) cells are essential for healthy immune responses to environmental proteins and successful AIT. Treg cells comprise different subsets of T cells with suppressive capacity, which control the development and maintenance of allergic diseases by various ways of action. Molecular mechanisms of generation of Treg cells, the identification of novel immunological organs, where this might occur in vivo, such as tonsils, and related epigenetic mechanisms are starting to be deciphered. The key role played by the suppressor cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β produced by functional Treg cells during the generation of immune tolerance to allergens is now well established. Treg and Breg cells together have a role in suppression of IgE and induction of IgG4 isotype allergen-specific antibodies particularly mediated by IL-10. Other cell types such as subsets of dendritic cells, NK-T cells and natural killer cells producing high levels of IL-10 may also contribute to the generation of healthy immune responses to allergens. In conclusion, better understanding of the immune regulatory mechanisms operating at different stages of allergic diseases will significantly help the development of better diagnostic and predictive biomarkers and therapeutic interventions.

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Acknowledgements

The laboratories of authors are supported by the Swiss National Foundation grants 320030_140772 and Christine Kühne—Center for Allergy Research and Education (CK-CARE), European 7th frame work projects MeDALL: Mechanisms of the Development of Allergy (No:261357) and PREDICTA: Post-Infectious Immune Reprogramming and Its Association with Persistence and Chronicity of Respiratory Allergic Diseases (No: 260895), Swiss Polish Research Grant, Spanish Ministerio de Economía y Competitividad MINECO (IPT-2012-0639-090000 and SAF2010-22198) and Comunidad de Madrid CAM (S2010/BMD-2353). OP is a Ramón y Cajal Scholar funded by MINECO and the European Social Fund. C Akdis has received research support from Novartis, PREDICTA: European Commission’s Seventh Framework programme No.260895, the Swiss National Science Foundation, MeDALL: European Commission's Seventh Framework Programme No. 261357, the Global Allergy and Asthma European Network, and the Christine Kühne-Center for Allergy Research and Education.

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Authors and Affiliations

  1. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland

    O Palomares, O Cavkaytar, M Akdis & C A Akdis

  2. Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain

    O Palomares

  3. Department of Organic Chemistry, School of Chemistry, Complutense University of Madrid, Madrid, Spain

    M Martín-Fontecha

  4. Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland

    R Lauener, C Traidl-Hoffmann & C A Akdis

  5. Cantonal Childrens Hospital, St Gallen, Switzerland

    R Lauener

  6. UNIKA-T, Institute for environmental medicine, Technische Universität Munich, Munich, Germany

    C Traidl-Hoffmann

  7. Department of Pediatric Allergology, School of Medicine, Hacettepe University, Ankara, Turkey

    O Cavkaytar

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  1. O Palomares
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Competing interests

C Akdis has consulted for Actellion, Aventis, Stallergenes and Allergopharma; is a pastpresident of the European Academy of Allergology and Clinical Immunology; is a fellow and interest group member of the American Academy of Allergy, Asthma and Immunology; is an ex-committee member of the Global Allergy and Asthma European Network; and is director of Christine Kühne-Center for Allergy Research and Education. The remaing authors declare no conflict of interest.

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Palomares, O., Martín-Fontecha, M., Lauener, R. et al. Regulatory T cells and immune regulation of allergic diseases: roles of IL-10 and TGF-β. Genes Immun 15, 511–520 (2014). https://doi.org/10.1038/gene.2014.45

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