Human eosinophils release IL-1ß and increase expression of IL-17A in activated CD4+ T lymphocytes

Authors

  • S. Esnault,

    Corresponding author
    • Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • E. A. B. Kelly,

    1. Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • L. M. Nettenstrom,

    1. Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA
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  • E. B. Cook,

    1. Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • C. M. Seroogy,

    1. Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA
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  • N. N. Jarjour

    1. Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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Correspondence:
Dr. Stephane Esnault, Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, 600 Highland Avenue, CSC K4/928, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-9988, USA. E-mail: sesnault@medicine.wisc.edu

Summary

Background

Differentiation and activation of CD4+ T cells is controlled by various cytokines produced by innate immune cells. We have shown that eosinophils (EOS) have the potential to influence Th1 and Th2 cytokine generation by CD4+ cells, but their influence on IL-17A (IL-17) has not been established.

Objective

The purpose of this study is to determine the effect of EOS on IL-17 production by lymphocytes.

Methods

Pre-activated CD4+ T cells were cultured in the presence of either autologous EOS or EOS culture supernatants. Expression of IL-17 was determined by real-time quantitative PCR (qPCR) after 5 h and protein level was measured after 48 h. To determine the effect of allergen-induced airway EOS on IL-17, subjects with mild allergic asthma underwent bronchoscopic segmental bronchoprovocation with allergen (SBP-Ag) after a treatment with an anti-IL-5 neutralizing antibody (mepolizumab) to reduce airway eosinophilia. IL-17 mRNA was measured in bronchoalveolar lavage (BAL) cells by qPCR.

Results

In vitro, EOS significantly increased IL-17 production by CD4+ T cells. Addition of exogenous IL-1ß increased expression of IL-17 mRNA by CD4+ T cells. EOS expressed and released IL-1ß. Furthermore, levels of IL-1ß in EOS supernatants highly correlated with their ability to increase IL-17 expression by CD4+ T cells, and neutralizing antibody to IL-1ß reduced expression of IL-17 mRNA. In vivo, reduction of EOS in the airway using mepolizumab was associated with diminished IL-17 expression after SBP-Ag.

Conclusions and clinical relevance

Our data demonstrate that EOS can promote IL-17 production through the release of IL-1ß. Enhanced IL-17 cytokine production is another mechanism by which EOS may participate in pathogenesis of allergic airway inflammation in asthma.

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