A.V. and F.N. equally contributed to the paper.
Poly(I:C) promotes the production of IL-17A by murine CD1d-driven invariant NKT cells in airway inflammation
Article first published online: 7 AUG 2012
© 2012 John Wiley & Sons A/S
Volume 67, Issue 10, pages 1223–1232, October 2012
How to Cite
To cite this article: Poly(I:C) promotes the production of IL-17A by murine CD1d-driven invariant NKT cells in airway inflammation. Allergy 2012; 67: 1223–1232., , , , , .
Edited by: Marek Sanak
- Issue published online: 13 SEP 2012
- Article first published online: 7 AUG 2012
- Manuscript Accepted: 19 JUN 2012
- Tuscany Region (Health Research Programme 2009)
- Italian Ministry of Education. Grant Number: PRIN 2009 project
- Italian Ministry of Health. Grant Number: Strategic Project 2008
- The Italian Association for Cancer Research (AIRC)
- Th17 response
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.
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.
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.
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.