IL-10-inducing adjuvants enhance sublingual immunotherapy efficacy in a murine asthma model.
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.
Van Overtvelt
Laurence
L
Research and Development, Stallergènes SA, Antony, France.
Lombardi
Vincent
V
Razafindratsita
Alain
A
Saint-Lu
Nathalie
N
Horiot
Stéphane
S
Moussu
Hélène
H
Mascarell
Laurent
L
Moingeon
Philippe
P
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
D000276:Adjuvants, Immunologic; D016753:Interleukin-10; D003907:Dexamethasone; D010047:Ovalbumin; D002117:Calcitriol