title: Effect of Mucosal Cytokine Administration on Selective Expansion of Vaginal Dendritic Cells to Support Nanoparticle Transport.
abstract: OBJECTIVE
  The capacity of antigen-carrying vaccine nanoparticles (NPs) administered vaginally to stimulate local immune responses may be limited by the relatively low numbers of antigen-presenting cells (APCs) in the genital mucosa. Because inflammation is associated with increased susceptibility to sexually transmitted infections, we sought to increase APC numbers without causing inflammation.
  
  
  METHODS
  In this study, we evaluated intravaginal delivery of chemokines, growth factors, or synthetic adjuvants to expand APCs in reproductive tissues.
  
  
  RESULTS
  We found that granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated expansion of CD11b+ dendritic cells (DCs) within 24 hr of intravaginal administration, with no effect on Langerhans cells or macrophages. Expansion of the CD11b+ DC population was not associated with increased inflammatory cytokine production, and these cells retained phagocytic function.
  
  
  CONCLUSIONS
  Our data suggest that non-inflammatory expansion of mucosal APCs by intravaginal GM-CSF could be used as an adjuvanting strategy to potentiate the genital immune response to nanoparticulate mucosal vaccines.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors.forename: Renuka
authors.initials: R
authors.lastname: Ramanathan
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors.forename: Jaehyung
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Hughes
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Lykins
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors.forename: Hunter R
authors.initials: HR
authors.lastname: Bennett
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.|Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Hladik
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Woodrow
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D001692:Biological Transport; D039481:CD11b Antigen / Q000378:metabolism; D018925:Chemokines / Q000494:pharmacology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism; D053758:Nanoparticles / Q000378:metabolism*; D014614:Vaccines, Synthetic / Q000276:immunology; D014621:Vagina / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D018925:Chemokines; C509295:ITGAM protein, human; D014614:Vaccines, Synthetic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Cellular expansion; GM-CSF; chemokines; dendritic cells; reproductive mucosa