title: IL-10-inducing adjuvants enhance sublingual immunotherapy efficacy in a murine asthma model.
abstract: BACKGROUND
  IL-10-inducing adjuvants could enhance the efficacy of allergy vaccines in establishing allergen-specific tolerance. The aim of this study was to identify such adjuvants using in vitro cultures of human and murine cells and to evaluate them in a therapeutic murine model of sublingual immunotherapy (SLIT).
  
  
  METHODS
  Adjuvants stimulating IL-10 gene expression by human or murine immune cells were tested sublingually in BALB/c mice sensitized to ovalbumin (OVA), assessing the reduction in airway hyperresponsiveness (AHR) by whole-body plethysmography. The induction of regulatory T cells (T(reg)) was evaluated using phenotypic and functional assays. T-cell proliferation in cervical lymph nodes (LNs) was assessed following intravenous transfer of CFSE-labelled OVA-specific T cells and FACS analysis.
  
  
  RESULTS
  A combination of 1,25-dihydroxyvitamin D3 plus dexamethasone (VitD3/Dex) as well as Lactobacillus plantarum were found to induce IL-10 production by human and murine dendritic cells (DCs). The former inhibits LPS-induced DC maturation, whereas L. plantarum induces DC maturation. Following stimulation with VitD3/Dex-pretreated DCs, CD4+ naïve T cells exhibit a T(reg) profile. In contrast, a Th1/T(reg) pattern of differentiation is observed in the presence of DCs treated with L. plantarum. Both adjuvants significantly enhance SLIT efficacy in mice, in association with either induction of Foxp3+ T(reg) cells (for VitD3/Dex) or proliferation of OVA-specific T cells in cervical LNs (for L. plantarum).
  
  
  CONCLUSIONS
  Both VitD3/Dex and L. plantarum polarize naïve T cells towards IL-10-expressing T cells, through distinct mechanisms. As adjuvants, they both enhance SLIT efficacy in a murine asthma model.
authors.affiliation: Research and Development, Stallergènes SA, Antony, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Van Overtvelt
authors.forename: Vincent
authors.initials: V
authors.lastname: Lombardi
authors.forename: Alain
authors.initials: A
authors.lastname: Razafindratsita
authors.forename: Nathalie
authors.initials: N
authors.lastname: Saint-Lu
authors.forename: Stéphane
authors.initials: S
authors.lastname: Horiot
authors.forename: Hélène
authors.initials: H
authors.lastname: Moussu
authors.forename: Laurent
authors.initials: L
authors.lastname: Mascarell
authors.forename: Philippe
authors.initials: P
authors.lastname: Moingeon
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000286:Administration, Sublingual; D000818:Animals; D001249:Asthma / Q000628:therapy*; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D003888:Desensitization, Immunologic; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D048191:Lactiplantibacillus plantarum / Q000276:immunology*; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000633:toxicity; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D016753:Interleukin-10; D003907:Dexamethasone; D010047:Ovalbumin; D002117:Calcitriol