Activation of T cells by dendritic cells exposed to a reference sensitizer: Towards a promising model to assess the allergenic potential of chemicals

Huppert, Cécile; Paris, Christophe; Langonné, Isabelle; Müller, S.; Mathiot, Julianne; Abdessadeq, Hakima; Gagnaire, François; Battais, F.; Sponne, Isabelle

doi:10.1111/cod.12991

Cited by 6 publications

(11 citation statements)

References 46 publications

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“…From a regulatory point of view, it is very relevant to be able to discriminate between Th1‐ and Th2‐oriented immune responses with a cell culture method. These data need to be confirmed by the use of a co‐culture model using BMDCs and T cells, 55 in order to assess the cytokines pattern of T‐cells co‐cultured with BMDCs exposed to BPA substitutes, as a read‐out of their differentiation state.…”

Section: Discussionmentioning

confidence: 99%

Identification of the allergenic sensitizing potential of bisphenol A substitutes used in the industry

Mourot‐Bousquenaud,

Langonné,

Buchheit

et al. 2023

Contact Dermatitis

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BackgroundBisphenol (BP‐)A is a chemical used in Europe to produce polycarbonate plastics and epoxy resin or as colour developer in thermal paper. Due to its toxicity, BPA presence was restricted by European regulations. Therefore, substitute chemicals are replacing BPA.ObjectiveTo assess the allergenic sensitizing potential of 27 substitutes to BPA used in the industry.MethodsThe expression of two costimulatory molecules and six cytokines were analysed by flow cytometry in mouse bone marrow‐derived dendritic cells (BMDCs) exposed to the chemicals.ResultsAll substances except one induced overexpression of at least one receptor and were thus identified as having allergenic sensitizing potential. Based on the BMDC model, they were classified as extreme (1 out of 27), strong (20 out of 27) and moderate (5 out of 27) sensitizers. BPA was classified as a moderate sensitizer and BPF was the only substitute classified as a non‐sensitizer. The more potent substitutes induced more than 2‐fold secretion of CCL3, CCL4 and/or CCL5 by dendritic cells.ConclusionMost of the BPA substitutes tested in this study have an allergenic sensitizing potential; 24 of them being more potent than BPA itself. Only BPE, BPF and 2,4‐BPS appeared to be weaker sensitizers than BPA.

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Section: Discussionmentioning

confidence: 99%

Identification of the allergenic sensitizing potential of bisphenol A substitutes used in the industry

Mourot‐Bousquenaud,

Langonné,

Buchheit

et al. 2023

Contact Dermatitis

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“…Indeed, depending on the mechanisms or products studied, these different DCs models are complementary to evaluate DC activation upon CS exposure. In this context, regarding the ability of BMDCs to activate T cells (TCs) in vitro, the BM-DCs model seems promising as it has recently been described to allow the classification of chemicals according to their allergenic potential (Battais et al, 2017;Huppert et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Models of Dendritic Cells to Assess Skin Sensitization

et al. 2022

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Allergic contact dermatitis (ACD) is a complex skin pathology occurring in reaction against environmental substances found in the workplace (cement, hair dyes, textile dyes), in the private environment (e.g., household products, cosmetic ingredients), or following skin exposure to drugs. Many cells are involved in the initiation of ACD during the sensitization phase. The four key events (KE) of skin sensitization AOP are covalent binding to skin proteins (KE1), keratinocyte activation (KE2), activation of DCs (KE3), and T-cell activation and proliferation (KE4), leading to the adverse outcome of ACD. Dendritic cells (DCs) are thus playing a key role in ACD pathophysiology. Indeed, in the presence of chemical sensitizers, DCs migrate from the skin to the draining lymph nodes and present peptide-chemical conjugates to T cells, leading to their activation and proliferation. In vitro methods have been actively developed to assess the activation of DCs by chemicals to establish a reliable in vitro sensitization test. Therefore, this review will detail the most used methods and protocols to develop DC models in vitro. Three different models of DCs will be addressed: 1) DCs derived from Cord Blood (CD34-DCs), 2) DCs derived from Monocytes (Mo-DCs), and 3) DCs derived from mice Bone-Marrow (BM-DCs). In addition, a model of exposition to contact sensitizers to assess KE3 of skin sensitization will be detailed for each of the models presented.

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“…T CD4 + (Th) lymphocytes were isolated from naïve BALB/cJRj mice, labeled with carboxyfluorescein succinimidyl ester (BD Biosciences) in order to study their proliferation, and added to the 96-well plates containing BMDCs (BMDC/Th lymphocyte ratio: 1:2) for 5 days. The protocol was adapted from an existing protocol . Cells were restimulated 5 h before the end of incubation with the respective gliadins used for priming (100 μg/mL) and Brefeldin A and Monensin (BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

“…The protocol was adapted from an existing protocol. 34 Cells were restimulated 5 h before the end of incubation with the respective gliadins used for priming (100 μg/mL) and Brefeldin A and Monensin (BD Biosciences). Cells were harvested and stained with antibodies directed to surface markers (CD3-APC-Cy7, CD44-BV421, and CD4-BV510; BD Biosciences) in the presence of mouse BD Fc Block (BD Biosciences).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Deamidation and Enzymatic Hydrolysis of Gliadins Alter Their Processing by Dendritic Cells in Vitro

Villemin

Tranquet

Solé-Jamault

et al. 2019

J. Agric. Food Chem.

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Gliadins are major wheat allergens. Their treatment by acid or enzymatic hydrolysis has been shown to modify their allergenic potential. As the interaction of food proteins with dendritic cells (DCs) is a key event in allergic sensitization, we wished to investigate whether deamidation and enzymatic hydrolysis influence gliadin processing by DC and to examine the capacity of gliadins to activate DCs. We compared the uptake and degradation of native and modified gliadins by DCs using mouse bone marrow-derived DCs. We also analyzed the effects of these interactions on the phenotypes of DCs and T helper (Th) lymphocytes. Modifying gliadins induced a change in physicochemical properties (molecular weight, hydrophobicity, and sequence) and also in the peptide size. These alterations in turn led to increased uptake and intracellular degradation of the proteins by DCs. Native gliadins (NGs) (100 μg/mL), but not modified gliadins, increased the frequency of DC expressing CD80 (15.41 ± 2.36% vs 6.81 ± 1.10%, p < 0.001), CCR7 (28.53 ± 8.17% vs 17.88 ± 2.53%, p < 0.001), CXCR4 (70.14 ± 4.63% vs 42.82 ± 1.96%, p < 0.001), and CCR7-dependent migration (2.46 ± 1.45 vs 1.00 ± 0.22, p < 0.01) compared with NGs. This was accompanied by Th lymphocyte activation (30.37 ± 3.87% vs 21.53 ± 3.14%, p < 0.1) and proliferation (16.39 ± 3.97% vs 9.31 ± 2.80%, p > 0.1). Moreover, hydrolysis decreases the peptide size and induces an increase in gliadin uptake and degradation. Deamidation and extensive enzymatic hydrolysis of gliadins modify their interaction with DCs, leading to alteration of their immunostimulatory capacity. These findings demonstrate the strong relationship between the biochemical characteristics of proteins and immune cell interactions.

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Activation of T cells by dendritic cells exposed to a reference sensitizer: Towards a promising model to assess the allergenic potential of chemicals

Abstract: The BMDCs used in this previously developed model appear to have the ability to activate TCs, confirming that the BMDC model represents a reliable assay for assessing the sensitizing potential of chemicals.

Cited by 6 publications

References 46 publications

Identification of the allergenic sensitizing potential of bisphenol A substitutes used in the industry

Identification of the allergenic sensitizing potential of bisphenol A substitutes used in the industry

Models of Dendritic Cells to Assess Skin Sensitization

Deamidation and Enzymatic Hydrolysis of Gliadins Alter Their Processing by Dendritic Cells in Vitro

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