title: Poly(I:C) promotes the production of IL-17A by murine CD1d-driven invariant NKT cells in airway inflammation.
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.
authors.affiliation: Immunoallergology Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Vultaggio
authors.forename: F
authors.initials: F
authors.lastname: Nencini
authors.forename: S
authors.initials: S
authors.lastname: Pratesi
authors.forename: G
authors.initials: G
authors.lastname: Petroni
authors.forename: S
authors.initials: S
authors.lastname: Romagnani
authors.forename: E
authors.initials: E
authors.lastname: Maggi
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D005699:Galactosylceramides / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D020381:Interleukin-17 / Q000096:biosynthesis*; D051379:Mice; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*
chemical_list: D055610:Antigens, CD1d; D005699:Galactosylceramides; D020381:Interleukin-17; C493154:alpha-galactosylceramide; D011070:Poly I-C