Filaggrin null mutations associate with increased frequencies of allergen-specific CD4+ T-helper 2 cells in patients with atopic eczema

Authors

  • T. McPherson,

    1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford and NIHR Biomedical Research Centre, OX3 9DS, U.K.
    2. Department of Dermatology, Churchill Hospital, Old Road, Oxford, OX3 7LJ, U.K.
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  • V.J. Sherman,

    1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford and NIHR Biomedical Research Centre, OX3 9DS, U.K.
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  • A. Aslam,

    1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford and NIHR Biomedical Research Centre, OX3 9DS, U.K.
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  • L. Crack,

    1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford and NIHR Biomedical Research Centre, OX3 9DS, U.K.
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  • H. Chan,

    1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford and NIHR Biomedical Research Centre, OX3 9DS, U.K.
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  • A. Lloyd-Lavery,

    1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford and NIHR Biomedical Research Centre, OX3 9DS, U.K.
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  • L. Jones,

    1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford and NIHR Biomedical Research Centre, OX3 9DS, U.K.
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  • M. Ardern-Jones,

    1. Department of Dermatology, University of Southampton, Southampton, U.K.
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  • G. Ogg

    1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford and NIHR Biomedical Research Centre, OX3 9DS, U.K.
    2. Department of Dermatology, Churchill Hospital, Old Road, Oxford, OX3 7LJ, U.K.
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  • Conflicts of interest
    None declared.

  • T.M. and V.J.S. contributed equally.

Tess McPherson.
E-mail: tess.mcpherson@imm.ox.ac.uk

Summary

Background  Filaggrin null mutations associate with atopic eczema and also with asthma when present with eczema. However, while epidermal dysfunction is an important factor in disease pathogenesis, it is unclear how such dysfunction interacts with immune responses to contribute to cutaneous and other inflammatory atopic disease.

Objectives  To gain a better understanding of the mechanisms underlying such predisposition in order to understand different disease phenotypes and possibly identify potential treatment targets.

Methods  We studied 33 individuals with atopic eczema and used interleukin-4 immunospot and human leucocyte antigen class II tetrameric complexes to investigate the peripheral blood allergen-specific CD4+ T-cell responses.

Results  Filaggrin null mutations associated with significantly (P < 0·05) higher frequencies of allergen-specific CD4+ T-helper 2 cell responses.

Conclusions  These data would support a model where barrier dysfunction possibly promotes greater allergen penetration and delivery to drive allergen-specific CD4+ T cells. This could further contribute to respiratory and cutaneous inflammatory disease.

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