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Clinical & Experimental Allergy

IL-17 eliminates therapeutic effects of oral tolerance in murine airway allergic inflammation

Authors

  • H. Kawakami,

    1. Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • T. Koya,

    Corresponding author
    • Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • H. Kagamu,

    1. Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • Y. Kimura,

    1. Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • H. Sakamoto,

    1. Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • C. Yamabayashi,

    1. Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • T. Furukawa,

    1. Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • T. Sakagami,

    1. Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • T. Miyabayashi,

    1. Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • T. Hasegawa,

    1. Department of General Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
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  • E. Suzuki,

    1. Department of General Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
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  • I. Narita

    1. Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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Correspondence:

Toshiyuki Koya, Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

E-mail: tkoya@med.niigata-u.ac.jp

Summary

Background

Oral tolerance is a classically used strategy for antigen-specific systemic immunotherapy. However, the roles of IL-17 in modification of oral tolerance are not yet understood.

Objective

To define the effects of IL-17 on the modification of oral tolerance, the effects of transfer of Th17 cells, administration of IL-17 or anti-IL-17 antibody (αIL-17Ab) to a murine allergic airway inflammation model were investigated.

Methods

Mice sensitized to and challenged with OVA, received OVA feeding, followed by OVA challenges. Transfer of Th17 cells, administration of IL-17 or αIL-17Ab were executed during OVA feeding. Airway hyperresponsiveness (AHR), airway inflammation, Th2 cytokine response and lung pathology were assessed.

Results

Administration of IL-17 as well as transfer of Th17 cells aggravated AHR and airway allergic inflammation as compared with the findings in mice subjected to OVA feeding alone, whereas administration of αIL-17Ab ameliorated AHR and airway eosinophilia. The effects of Th17 transfer were presumably attributable to augmentation of endogenous IL-6 production in gut. The number of Foxp3-positive regulatory T (Treg) cells in lungs and Payer's patches was increased in the OVA fed mice, whereas the number of these cells was decreased in the mice subjected to OVA feeding + Th17 cell transfer. Neutralization of IL-6 by monoclonal antibody in the mice subjected to OVA feeding + transfer of Th17 cells restored the effects of oral tolerance.

Conclusions and Clinical Relevance

These data suggest that IL-17 may inhibit the induction of tolerance to antigen through, at least in part augmenting IL-6 production, thereby suppressing the expansion of Treg cells.

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