title: Serum amyloid A promotes lung neutrophilia by increasing IL-17A levels in the mucosa and γδ T cells.
abstract: BACKGROUND
  Neutrophilic inflammation is an important pathologic feature of chronic obstructive pulmonary disease (COPD) and infectious exacerbations of COPD. Serum amyloid A (SAA) promotes neutrophilic inflammation by its interaction with lung mucosal ALX/FPR2 receptors. However, little is known about how this endogenous mediator regulates IL-17A immunity.
  
  
  OBJECTIVE
  To determine whether SAA causes neutrophilic inflammation by IL-17A-dependent mechanisms.
  
  
  METHODS
  The relationship between SAA and neutrophils was investigated in lung sections from patients with COPD and a chronic mouse model of SAA exposure. A neutralizing antibody to IL-17A was used to block SAA responses in vivo, and a cell-sorting strategy was used to identify cellular sources.
  
  
  RESULTS
  SAA mRNA expression was positively associated with tissue neutrophils in COPD (P < 0.05). SAA predominately promoted expression of the TH17 polarizing cytokine IL-6, which was opposed by 15-epi-lipoxin A4, a counter-regulatory mediator, and ALX/FPR2 ligand. SAA-induced inflammation was markedly reduced by a neutralizing antibody to IL-17A in vivo. Cellular sources of IL-17A induced by SAA include CD4(+) T cells, γδ T cells, and an Epcam(+)CD45(-) population enriched for epithelial cells. SAA promotes expression of IL-17A in γδ T cells and this innate cell proportionally expressed higher levels of IL-17A transcript than CD4(+) T cells or epithelial cells.
  
  
  CONCLUSIONS
  The SAA-IL-17A axis represents an important innate defense network that may underlie persistent neutrophilic airway inflammation in COPD and modulating the ALX/FPR2 receptor represents a novel approach to targeting aberrant IL-17A-mediated lung immunity.
authors.affiliation: Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Desiree
authors.initials: D
authors.lastname: Anthony
authors.forename: Huei Jiunn
authors.initials: HJ
authors.lastname: Seow
authors.forename: Mohib
authors.initials: M
authors.lastname: Uddin
authors.forename: Michelle
authors.initials: M
authors.lastname: Thompson
authors.forename: Lovisa
authors.initials: L
authors.lastname: Dousha
authors.forename: Ross
authors.initials: R
authors.lastname: Vlahos
authors.forename: Louis B
authors.initials: LB
authors.lastname: Irving
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Levy
authors.forename: Gary P
authors.initials: GP
authors.lastname: Anderson
authors.forename: Steven
authors.initials: S
authors.lastname: Bozinovski
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000097:blood / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology*; D051379:Mice; D020556:Neutrophil Infiltration / Q000502:physiology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology; D000685:Serum Amyloid A Protein / Q000032:analysis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D020381:Interleukin-17; D000685:Serum Amyloid A Protein