Allergic contact dermatitis: is the reactive chemistry of skin sensitizers the whole story? A response

Roberts, David W.

doi:10.1111/cod.12057

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…Most skin sensitizers are low-molecular-weight xenobiotic chemicals that bind covalently to skin proteins through a Michael addition, Schiff base formation, bimolecular nucleophilic substitution (S N 2), nucleophilic aromatic substitution (S N Ar), or acyl transfer (Aptula and Roberts 2006;Chipinda et al 2011;Enoch et al 2011;Roberts 2013). Another type of common sensitizers is metals that form coordination complexes with skin proteins and, in the case of nickel, can directly interact with receptors (e.g.…”

Section: Introductionmentioning

confidence: 99%

Computational approaches for skin sensitization prediction

Wilm

Kühnl

Kirchmair

2018

Critical Reviews in Toxicology

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Drugs, cosmetics, preservatives, fragrances, pesticides, metals, and other chemicals can cause skin sensitization. The ability to predict the skin sensitization potential and potency of substances is therefore of enormous importance to a host of different industries, to customers' and workers' safety. Animal experiments have been the preferred testing method for most risk assessment and regulatory purposes but considerable efforts to replace them with non-animal models and in silico models are ongoing. This review provides a comprehensive overview of the computational approaches and models that have been developed for skin sensitization prediction over the last 10 years. The scope and limitations of rule-based approaches, read-across, linear and nonlinear (quantitative) structure-activity relationship ((Q)SAR) modeling, hybrid or combined approaches, and models integrating computational methods with experimental results are discussed followed by examples of relevant models. Emphasis is placed on models that are accessible to the scientific community, and on model validation. A dedicated section reports on comparative performance assessments of various approaches and models. The review also provides a concise overview of relevant data sources on skin sensitization.

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Section: Introductionmentioning

confidence: 99%

Computational approaches for skin sensitization prediction

Wilm

Kühnl

Kirchmair

2018

Critical Reviews in Toxicology

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“…It has been found that depending on the reaction mechanism of the protein-binding step there are different relationships between model reactivity parameters and potency. − This is argued to be because, depending on the reaction mechanism, relative reactivities toward the several nucleophilic protein sites will differ. Thus, for example, the Schiff category chemicals probably sensitize via reaction with amino groups of proteins, whereas the Michael acceptor category chemicals probably sensitize via reaction with protein thiol groups.…”

Section: Resultsmentioning

confidence: 99%

Mechanism-Based QSAR Modeling of Skin Sensitization

Dearden

Hewitt

Roberts

et al. 2015

Chem. Res. Toxicol.

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“…soaps, perfumes, solvents) 4 . Exposure to low molecular weight haptens can induce an adaptive immune response resulting in allergic contact dermatitis (ACD) [4][5][6][7] . In the sensitization phase of ACD, antigenpresenting cells in the skin get activated.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Effects of Nanoparticles on Dendritic Cells in a Model of Allergic Contact Dermatitis - Importance of PD-L2 Expression

Lau

Pineda

DeLouise

2023

Preprint

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Nanoparticle (NP) skin exposure is linked to the increased prevalence of allergic contact dermatitis. In prior studies using the mouse contact hypersensitivity (CHS) model, we reported that silica 20 nm (Si20nm) suppressed the allergic response and TiO2 doped with manganese (mTiO2) exacerbated it. In this work, we conducted in vitro experiments using bone marrow-derived dendritic cells (BMDCs) to study the combinatorial effect of the potent 2, 4-dinitrofluorobenzene (DNFB) hapten sensitizer with Si20nm and mTiO2 NPs on BMDC cytotoxicity, cytokine secretion and phenotype using the B7 family ligands. Results show that DNFB and mTiO2 behave similarly and exhibit proinflammatory characteristics while Si20nm promotes a naive phenotype. We observe that the B7-H3 (CD276) ligand is only expressed on CD80+ (B7-1) BMDC. Results from adoptive transfer CHS studies, combined with BMDC phenotype analysis, point to the importance of PD-L2 expression in modulating the adaptive immune response. This work identifies metrics that can be used to predict the effects of NPs on contact allergy and to guide efforts to engineer cell-based therapies to induce antigen specific immune tolerance.

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Allergic contact dermatitis: is the reactive chemistry of skin sensitizers the whole story? A response

Cited by 4 publications

References 20 publications

Computational approaches for skin sensitization prediction

Computational approaches for skin sensitization prediction

Mechanism-Based QSAR Modeling of Skin Sensitization

Immunomodulatory Effects of Nanoparticles on Dendritic Cells in a Model of Allergic Contact Dermatitis - Importance of PD-L2 Expression

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