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Impaired ICOSL in human myeloid dendritic cells promotes Th2 responses in patients with allergic rhinitis and asthma

Authors

  • C. Shen,

    1. Pôle Pneumologie, ORL & Dermatologie, Institut de Recherche Expérimentale & Clinique (IREC), Université Catholique de Louvain (UCL), Brussels, Belgium
    2. Institute for Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Cliniques Universitaires St-Luc, Brussels, Belgium
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  • C. Hupin,

    1. Pôle Pneumologie, ORL & Dermatologie, Institut de Recherche Expérimentale & Clinique (IREC), Université Catholique de Louvain (UCL), Brussels, Belgium
    2. Institute for Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Cliniques Universitaires St-Luc, Brussels, Belgium
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    • Joint authors.
  • A. Froidure,

    1. Pôle Pneumologie, ORL & Dermatologie, Institut de Recherche Expérimentale & Clinique (IREC), Université Catholique de Louvain (UCL), Brussels, Belgium
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    • Joint authors.
  • B. Detry,

    1. Pôle Pneumologie, ORL & Dermatologie, Institut de Recherche Expérimentale & Clinique (IREC), Université Catholique de Louvain (UCL), Brussels, Belgium
    2. Institute for Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Cliniques Universitaires St-Luc, Brussels, Belgium
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  • C. Pilette

    Corresponding author
    1. Pôle Pneumologie, ORL & Dermatologie, Institut de Recherche Expérimentale & Clinique (IREC), Université Catholique de Louvain (UCL), Brussels, Belgium
    2. Institute for Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Cliniques Universitaires St-Luc, Brussels, Belgium
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  • Key points: This study shows an impaired ICOSL expression by human myeloid dendritic cells, which contributes to biased Th2 polarization in allergic rhinitis.

Summary

Background

Myeloid dendritic cells (mDCs) and costimulatory molecules such as ICOSL/B7H2 play a pivotal role in murine experimental asthma, while little is known in human allergic disease.

The aim of this study was to characterize the phenotype and ICOSL expression of mDCs from allergic rhinitis patients (AR) and their functional correlates on mDC regulation of T cell responses.

Methods

Human blood myeloid, CD1c+ DCs were isolated from AR or healthy controls. Expression of costimulatory molecules inducible costimulatory ligand (ICOSL) and programmed death ligand 1 (PD-L1) was analysed in blood mDCs by flow cytometry and in nasal tissue biopsies by dual immunostaining. Blood mDCs were cocultured with (allogeneic) CD4+ T cells before immunoassays for cytokine responses.

Results

mDCs from AR patients expressed a lower level of ICOSL, in both blood and nasal tissue. mDCs from AR were constitutively primed to induce Th2 cytokines and TNF in allogeneic CD4+ T cells, while no difference was observed for IFN-γ or IL-10. Production of IL-10 and IL-12 did not differ between AR and control mDCs. Blockade of ICOSL in control DCs up-regulated IL-13 but not IFN-γ in cocultures with T cells, while PD-L1 blockade up-regulated both IL-13 and IFN-γ.

Conclusions

Our data show that mDCs from patients with AR display impaired expression of ICOSL, and this defect licenses mDCs to promote aberrant IL-13- and IL-5-producing Th2 cell responses.

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