Poly(I:C) promotes the production of IL-17A by murine CD1d-driven invariant NKT cells in airway inflammation

Authors

  • A. Vultaggio,

    1. Immunoallergology Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy
    Search for more papers by this author
    • A.V. and F.N. equally contributed to the paper.
  • F. Nencini,

    1. Centre of Research, Transfer and High Education DENOTHE, University of Florence, Florence, Italy
    2. Department of Internal Medicine, University of Florence, Florence, Italy
    Search for more papers by this author
    • A.V. and F.N. equally contributed to the paper.
  • S. Pratesi,

    1. Centre of Research, Transfer and High Education DENOTHE, University of Florence, Florence, Italy
    2. Department of Internal Medicine, University of Florence, Florence, Italy
    Search for more papers by this author
  • G. Petroni,

    1. Centre of Research, Transfer and High Education DENOTHE, University of Florence, Florence, Italy
    2. Department of Internal Medicine, University of Florence, Florence, Italy
    Search for more papers by this author
  • S. Romagnani,

    1. Centre of Research, Transfer and High Education DENOTHE, University of Florence, Florence, Italy
    2. Department of Internal Medicine, University of Florence, Florence, Italy
    Search for more papers by this author
  • E. Maggi

    Corresponding author
    1. Centre of Research, Transfer and High Education DENOTHE, University of Florence, Florence, Italy
    2. Department of Internal Medicine, University of Florence, Florence, Italy
    • Immunoallergology Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy
    Search for more papers by this author

  • Edited by: Marek Sanak

Correspondence

Dr. Enrico Maggi, MD, Immunoallergology Unit, Centre for Research, Transfer and High Education ‘DENOTHE’, University of Florence, Policlinico di Careggi, Viale Morgagni, 85, 50134 Firenze, Italy.

Tel.: +39-055-4271049

Fax: +39-055-4271028

E-mail: e.maggi@dmi.unifi.it

Abstract

Background

IL-17A is associated with different asthma phenotypes as virus-associated or steroid-resistant asthma. Invariant natural killer T (iNKT) cells play an important role in the pathogenesis of asthma. The aim of the study was to evaluate the activity of polyinosinic–polycytidylic acid [poly(I:C)] on IL-17A production by CD1d-activated iNKT cells.

Methods

We analysed the in vitro effect of poly(I:C) on the release of IL-17A by spleen and lung CD1d-activated iNKT cells with α-galactosylceramide (α-GalCer). Its activity was also investigated in an α-GalCer-induced murine models, including lung inflammation. The inhibition of IL-17A by Toll-like receptor (TLR) 7 agonists in the same in vitro and in vivo models has been analysed.

Results

Poly(I:C) upregulated the in vitro IL-17A production by CD1d-activated NK1.1− CD4− iNKT subset, without modifying type 1 and type 2 cytokines. The two stimuli selectively upregulated IL-17A serum levels in vivo. Their intratracheal administration resulted in increased airway hyper-reactivity (AHR), neutrophilia in bronchoalveolar lavage and airway inflammation, which were inhibited by anti-IL-17A antibody. Poly(I:C) effects were attributable to IL1β and IL-23 release from dendritic cells, as showed by inhibition with neutralizing antibodies. TLR7 agonists inhibited the IL-17A production by poly(I:C) plus α-GalCer in the same models. Such effect was associated with the increased production by DC of IL-17A-inhibiting cytokines and the dampening of IL-1β and IL-23.

Conclusions

Synthetic dsRNA selectively expand a CD1d-driven IL-17A-producing iNKT cell subset, thus explaining the worsening of airway inflammation by some viral infections. TLR3- and TLR7-triggering viral sequences can exert variable and opposite effects on adaptive immune response.

Ancillary