title: IL-17A inhibits airway reactivity induced by respiratory syncytial virus infection during allergic airway inflammation.
abstract: BACKGROUND
  Viral infections are the most frequent cause of asthma exacerbations and are linked to increased airway reactivity (AR) and inflammation. Mice infected with respiratory syncytial virus (RSV) during ovalbumin (OVA)-induced allergic airway inflammation (OVA/RSV) had increased AR compared with OVA or RSV mice alone. Furthermore, interleukin 17A (IL-17A) was only increased in OVA/RSV mice.
  
  
  OBJECTIVE
  To determine whether IL-17A increases AR and inflammation in the OVA/RSV model.
  
  
  METHODS
  Wild-type (WT) BALB/c and IL-17A knockout (KO) mice underwent mock, RSV, OVA or OVA/RSV protocols. Lungs, bronchoalveolar lavage (BAL) fluid and/or mediastinal lymph nodes (MLNs) were harvested after infection. Cytokine expression was determined by ELISA in the lungs or BAL fluid. MLNs were restimulated with either OVA (323-229) peptide or RSV M2 (127-135) peptide and IL-17A protein expression was analysed. AR was determined by methacholine challenge.
  
  
  RESULTS
  RSV increased IL-17A protein expression by OVA-specific T cells 6 days after infection. OVA/RSV mice had decreased interferon-β protein expression compared with RSV mice. OVA/RSV mice had increased IL-23p19 mRNA expression in lung homogenates compared with mock, OVA or RSV mice. Unexpectedly, IL-17A KO OVA/RSV mice had increased AR compared with WT OVA/RSV mice. Furthermore, IL-17A KO OVA/RSV mice had increased eosinophils, lymphocytes and IL-13 protein expression in BAL fluid compared with WT OVA/RSV mice.
  
  
  CONCLUSIONS
  IL-17A negatively regulated AR and airway inflammation in OVA/RSV mice. This finding is important because IL-17A has been identified as a potential therapeutic target in asthma, and inhibiting IL-17A in the setting of virally-induced asthma exacerbations may have adverse consequences.
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. dawn.newcomb@vanderbilt.edu
authors: Dawn Catherine
authors: DC
authors: Newcomb
authors: Madison G
authors: MG
authors: Boswell
authors: Sara
authors: S
authors: Reiss
authors: Weisong
authors: W
authors: Zhou
authors: Kasia
authors: K
authors: Goleniewska
authors: Shinji
authors: S
authors: Toki
authors: Melissa T
authors: MT
authors: Harintho
authors: Nicholas W
authors: NW
authors: Lukacs
authors: Jay K
authors: JK
authors: Kolls
authors: R Stokes
authors: RS
authors: Peebles
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D012333:RNA, Messenger
keywords: Allergic lung disease; Asthma; Cytokine Biology; Respiratory Infection