Targeting Dendritic Cells in Allergen Immunotherapy

Novak, Natalija

doi:10.1016/j.iac.2006.02.010

Cited by 28 publications

(25 citation statements)

References 77 publications

(90 reference statements)

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“…Supporting this route also for PM‐allergoids is the response obtained in submandibular LNs, the primary draining lymph nodes of sublingual tissue 24. In this sense, besides antigen penetration across the sublingual epithelial barrier, an active capture by intraepithelial DCs25 or through the ductal epithelial cells26 has been described, even for particulate antigens, silica beads, or microbes 26. In fact, bigger structures than PM‐allergoids, like particles of different sizes15, 27 or whole cell bacteria,28, 29 have also been successfully used for immunization through the sublingual route.…”

Section: Discussionmentioning

confidence: 91%

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Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice

Soria

López-Relaño

Viñuela

et al. 2018

Allergy

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BackgroundPolymerized allergoids coupled to nonoxidized mannan (PM‐allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM‐allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM‐allergoids administered sublingually in comparison with native allergens.MethodsThree immunization protocols (4‐8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells.ResultsA quick antibody response and higher IgG2a/IgE ratio were observed with PM‐allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL‐4 ratio with a quick IL‐10 production by submandibular LN cells. An increase in CD4+ CD25high FOXP3+ Treg cells was detected in LNs and spleen of mice treated with PM‐allergoids. These allergoids were better captured than native allergens by antigen‐presenting (CD45+ MHC‐II +) cells obtained from the sublingual mucosa, including DCs (CD11b+) and macrophages (CD64+). Importantly, all the differential effects induced by PM‐allergoids were abolished when using oxidized instead of nonoxidized PM‐allergoids.ConclusionOur results demonstrate for the first time that PM‐allergoids administered through the sublingual route promote the generation of Th1 and FOXP3+ Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen‐presenting cells.

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Section: Discussionmentioning

confidence: 91%

“…Several mechanisms have been proposed for allergen uptake by DCs in SLIT, including the capture through specific IgE bound to FcεRI on oral Langerhans cells, a major DC population within the oral mucosa in human beings 25. In the case of PM‐allergoids, however, their low IgE binding reactivity16, 17, 18 would make this mechanism unlikely.…”

Section: Discussionmentioning

confidence: 99%

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice

Soria

López-Relaño

Viñuela

et al. 2018

Allergy

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“…As part of the development of nanoparticle (NP)-vaccines for the treatment of cancer, infectious diseases and allergies, many efforts have focused on dendritic cell (DC) targeting [1][2][3] . DCs are one of the most potent types of antigen presenting cell (APC) and are seen as key players in the initiation and control of adaptive immune responses [4][5] .…”

Section: Introductionmentioning

confidence: 99%

Multivalent Glycosylation of Fluorescent Gold Nanoclusters Promotes Increased Human Dendritic Cell Targeting via Multiple Endocytic Pathways

Guével

Perrino

Fernández³

et al. 2015

ACS Appl. Mater. Interfaces

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We report the synthesis and characterisation of gold nanoclusters (Au NCs) stabilised by a mixture of zwitterionic and multivalent mannose ligands. Characterisation of this carbohydrated nanosystem confirms its small size (~2 nm), intense red-NIR fluorescence, relatively high affinity to lectin (ConA), and stability in physiological media. Cell studies performed using human monocyte-derived dendritic cells (DCs) show that Au NC uptake efficiency is greatly enhanced by the presence of surface carbohydrate (> 250% compared to non-carbohydrated Au 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 2 NCs) allowing their detection in cells by fluorescence following incubation with concentrations as low as 1 µg.mL -1 . Investigation using electron microscopy and pharmacological inhibitorsindicates that Au NC uptake is mediated by multiple endocytic pathways involving the engulfment of Au NCs into endosomes and partial transport to lysosomes. Results show that clathrin and F-actin dependent pathways play major roles in Au NC uptake by DCs regardless of whether or not they are coated with carbohydrates. In contrast, a specific C-lectin inhibitor induces a 60% decrease in DC particle uptake only for the carbohydrate-coated Au NCs. This study demonstrates that the combination of ultra-small gold NCs and functionalisation with multivalent mannose ligands results in greatly enhanced human DC targeting, presumably due to increased diffusion and target cell binding, respectively.

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“…In this regard, adjuvants specifically selected for the sublingual route are particularly interesting, since Langerhans-like DCs in the oral mucosa are prone to produce IL-10 and TGF-β [21, 22]. In addition, oral Langerhans-like DCs induce IL-10- and TGF-β-producing T cells and secrete chemokines recruiting T reg in vitro [23]. …”

Section: Introductionmentioning

confidence: 99%

IL-10-Inducing Adjuvants Enhance Sublingual Immunotherapy Efficacy in a Murine Asthma Model

Overtvelt¹,

Lombardi²,

Razafindratsita³

et al. 2007

Int Arch Allergy Immunol

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Background: IL-10-inducing adjuvants could enhance the efficacy of allergy vaccines in establishing allergen-specific tolerance.The aim of this study wasto 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.

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Targeting Dendritic Cells in Allergen Immunotherapy

Cited by 28 publications

References 77 publications

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice

Multivalent Glycosylation of Fluorescent Gold Nanoclusters Promotes Increased Human Dendritic Cell Targeting via Multiple Endocytic Pathways

IL-10-Inducing Adjuvants Enhance Sublingual Immunotherapy Efficacy in a Murine Asthma Model

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