The hair dyes PPD and PTD fail to induce a T<sub>H</sub>2 immune response following repeated topical application in BALB/c mice

Rothe, Helga; Sarlo, Katherine; Scheffler, Heike; Goebel, Carsten

doi:10.3109/1547691x.2010.543096

Cited by 7 publications

(8 citation statements)

References 44 publications

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“…3.5 | IL-9 plays a protective role in a model of PPDinduced ACD To examine the role of IL-9 in PPD-induced ACD, we used a mouse model adapted from a previous model. 16 We treated Il9r-deficient mice with PPD, and they showed aggravated development of CHS, with more ear swelling than PPD-treated WT littermates ( Figure 6A). This aggravation was accompanied by more acanthosis and higher crust percentages ( Figure 6B-D).…”

Section: Il-9 Expression Is Increased In Pbmcs After Stimulationmentioning

confidence: 99%

“…For instance, in allergy to PPD, ear swelling induced by topical PPD application was shown to be lower in STAT6 −/− mice deficient for Th2 cytokines than in wild‐type (WT) mice, showing that Th2 cytokines play an essential role in ACD induction . Conversely, other authors failed to induce a Th2 response following repeated topical PPD application in mice, and concluded that exposure to hair dyes was not associated with relevant Th2 induction …”

Section: Introductionmentioning

confidence: 99%

“…15 Conversely, other authors failed to induce a Th2 response following repeated topical PPD application in mice, and concluded that exposure to hair dyes was not associated with relevant Th2 induction. 16 Some importance has also been attributed to Th17 cells, which constitute a subpopulation implicated in the pathogenesis of various allergic disorders, including ACD. 17,18 In a murine model of allergy to PPD, a trend towards a systemic increase in IL-17A expression was observed.…”

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confidence: 99%

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Increased expression of interleukin‐9 in patients with allergic contact dermatitis caused by p‐phenylenediamine

et al. 2018

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Background: Allergic contact dermatitis has been described as a type IV reaction caused by antigen-specific T cells. Central roles for CD8 + cytotoxic T cells as effector cells and CD4 + T cells as regulatory cells have been suggested. T helper (Th) 2 and Th1 cytokines have been implicated; however, the nature of the allergen influences the Th response.Objective: To determine the types of T cells and cytokines expressed in patients allergic to p-phenylenediamine (PPD).Methods: Serial skin biopsies of areas with positive patch test reactions in 29 PPD-sensitized patients were collected. T cell markers and cytokine expression were analysed by flow cytometry and quantitative reverse transcription polymerase chain reaction in both skin and peripheral blood mononuclear cells (PBMCs) of sensitized patients. Results:We observed increased expression of T cell markers and Th2/Th9-associated cytokines in both skin and stimulated PBMCs of PPD-allergic patients. Moreover, interleukin (IL)-9 was mainly produced by Th9 cells, in both skin and PBMCs. Further investigations showed that Il9rdeficient mice were more affected in a PPD contact hypersensitivity model than wild-type mice. Conclusion:We did not confirm the preclinical presence of CD8 + T cells. However, the expression of different T cell markers positively correlated with patch test reactions. IL-9 expression was strongly upregulated and directly related to patch test severity. In addition, we showed that IL-9 has an anti-inflammatory role in a mouse model of PPD contact hypersensitivity.

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Section: Il-9 Expression Is Increased In Pbmcs After Stimulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Increased expression of interleukin‐9 in patients with allergic contact dermatitis caused by p‐phenylenediamine

et al. 2018

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“…For example, human studies reveal PPD to be a respiratory sensitizer, 132 but it does not cause a Th2 cytokine response in mice. 133 Specific IgE is induced in some subjects, but not in others, particularly for diisocyanate sensitization. Thus, it is unclear whether IgE is mandatory or not.…”

Section: Evaluation Of the Aopmentioning

confidence: 99%

An Adverse Outcome Pathway for Sensitization of the Respiratory Tract by Low-Molecular-Weight Chemicals: Building Evidence to Support the Utility ofIn VitroandIn SilicoMethods in a Regulatory Context

Sullivan

Enoch

Ezendam

et al. 2017

Applied In Vitro Toxicology

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Sensitization of the respiratory tract is an important occupational health challenge, and understanding the mechanistic basis of this effect is necessary to support the development of toxicological tools to detect chemicals that may cause it. Here we use the adverse outcome pathway (AOP) framework to organize information that may better inform our understanding of sensitization of the respiratory tract, building on a previously published skin sensitization AOP, relying on literature evidence linked to low-molecular-weight organic chemicals and excluding other known respiratory sensitizers acting via different molecular initiating events. The established key events (KEs) are as follows: (1) covalent binding of chemicals to proteins, (2) activation of cellular danger signals (inflammatory cytokines and chemokines and cytoprotective gene pathways), (3) dendritic cell activation and migration, (4) activation, proliferation, and polarization of T cells, and (5) sensitization of the respiratory tract. These events mirror the skin sensitization AOP but with specific differences. For example, there is some evidence that respiratory sensitizers bind preferentially to lysine moieties, whereas skin sensitizers bind to both cysteine and lysine. Furthermore, exposure to respiratory sensitizers seems to result in cell behavior for KEs 2 and 3, as well as the effector T cell response, in general skewing toward cytokine secretions predominantly associated with T helper 2 (Th2) response. Knowledge gaps include the lack of understanding of which KE(s) drive the Th2 polarization. The construction of this AOP may provide insight into predictive tests that would in combination support the discrimination of respiratory-sensitizing from non-and skin-sensitizing chemicals, a clear regulatory need.

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“…In contrast, none of the more highly sensitized individuals (the +++ reactors in Table 1) continue to dye their hair, because of the strength of the allergic reaction that they experience. Very occasionally, p ‐phenylenediamine has even been reported to produce anaphylactic‐type reactions, albeit extremely rarely (reviewed in 37). The interesting question is whether skin sensitizing chemicals of lower potency can also be associated with the elicitation of severe reactions.…”

Section: The Clinical Expression Of Severity In Humansmentioning

confidence: 99%

Assessing the severity of allergic reactions: a regulatory dilemma

2012

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SummaryThe identification of chemicals possessing the intrinsic ability to cause sensitization via skin contact or inhalation, commonly referred to as skin and respiratory sensitizers, is a key endpoint in regulatory toxicology. Predictive assays for this purpose exist only for skin sensitizers, but, for both types of sensitizer, human evidence can be used to determine whether a substance should be classified. Furthermore, the use of human evidence for subcategorization according to sensitization potency is also accommodated within the regulations. Normally, this is based on the prevalence of sensitization in relation to the degree of exposure in the context of the size of the population exposed. However, the regulations also indicate that the severity of (allergic) reactions may be taken into account. In this article, we consider whether this is appropriate and whether there is evidence that reaction severity can inform decisions on classification and/or potency categorization. The conclusion drawn is that the severity of an allergic reaction does not correlate with, or serve as an indicator of, the sensitizing potency of a chemical. In reality, it reflects the overall extent of sensitization that an individual has acquired, in concert with the concentration of the causative allergen to which they have been exposed.

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The hair dyes PPD and PTD fail to induce a T_H2 immune response following repeated topical application in BALB/c mice

Cited by 7 publications

References 44 publications

Increased expression of interleukin‐9 in patients with allergic contact dermatitis caused by p‐phenylenediamine

Increased expression of interleukin‐9 in patients with allergic contact dermatitis caused by p‐phenylenediamine

An Adverse Outcome Pathway for Sensitization of the Respiratory Tract by Low-Molecular-Weight Chemicals: Building Evidence to Support the Utility ofIn VitroandIn SilicoMethods in a Regulatory Context

Assessing the severity of allergic reactions: a regulatory dilemma

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The hair dyes PPD and PTD fail to induce a TH2 immune response following repeated topical application in BALB/c mice

Cited by 7 publications

References 44 publications

Increased expression of interleukin‐9 in patients with allergic contact dermatitis caused by p‐phenylenediamine

Increased expression of interleukin‐9 in patients with allergic contact dermatitis caused by p‐phenylenediamine

An Adverse Outcome Pathway for Sensitization of the Respiratory Tract by Low-Molecular-Weight Chemicals: Building Evidence to Support the Utility ofIn VitroandIn SilicoMethods in a Regulatory Context

Assessing the severity of allergic reactions: a regulatory dilemma

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The hair dyes PPD and PTD fail to induce a T_H2 immune response following repeated topical application in BALB/c mice