Danger, intracellular signaling, and the orchestration of dendritic cell function in skin sensitization

Ainscough, Joseph S.; Gerberick, G. Frank; Dearman, Rebecca J.; Kimber, Ian

doi:10.3109/1547691x.2012.711782

Cited by 40 publications

(41 citation statements)

References 87 publications

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“…7,26 Several papers have shown an important role for the signalling of nucleotide-binding domain leucine-rich-repeat-containing receptors in ACD through activation of caspase-1 and subsequent expression of IL-1b. 7,26 Several papers have shown an important role for the signalling of nucleotide-binding domain leucine-rich-repeat-containing receptors in ACD through activation of caspase-1 and subsequent expression of IL-1b.…”

Section: Immune Mechanisms Of Allergic Contact Dermatitis Incorporatimentioning

confidence: 99%

“…[27][28][29][30] For example, NLRP3-deficient mice display an impaired response to skin sensitizers. 26 Martin's group demonstrated that contact sensitizers induce reactive oxygen species, which in turn generate DAMP molecules such as low-molecular-weight fragments of hyaluronic acid, which can activate TLR4. 26 Martin's group demonstrated that contact sensitizers induce reactive oxygen species, which in turn generate DAMP molecules such as low-molecular-weight fragments of hyaluronic acid, which can activate TLR4.…”

Section: Immune Mechanisms Of Allergic Contact Dermatitis Incorporatimentioning

confidence: 99%

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Why does allergic contact dermatitis exist?

McFadden

Puangpet

Basketter

et al. 2013

British Journal of Dermatology

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The skin immune system's propensity to produce allergic contact dermatitis (ACD) to harmless chemicals, while otherwise being an efficient defence system, represents a dermatological paradox. We postulate that a major role in signalling in ACD is played by Toll-like receptor (TLR)2 and TLR4, and arises from their activation by extracellular danger-associated molecular patterns (DAMPs). Ligand activation of TLR4/2 results in the expression of interleukins (ILs) IL-1β, IL-6, IL-12, IL-18 and IL-23, tumour necrosis factor-α and interferon-α. These cytokines promote acquisition of sensitization, and facilitate elicitation of contact allergy via multiple mechanisms, including the recruitment of CD4+ Th1 and Th17 cells. As Th1 cells secrete large amounts of DAMPs, a DAMP immune circuit (positive-feedback loop) is created. This is an important driver of skin sensitization and skin inflammation. Pathogenic extracellular bacteria, but not commensal bacteria, produce pathogen-associated molecular pattern molecules, which stimulate the expression of Th1- and Th17-promoting cytokines via TLR2 and TLR4. This also induces an immune circuit. The ability of the skin immune system to activate host defence mechanisms and to distinguish between pathogenic bacteria and commensals provides an explanation for why skin sensitization and ACD develop, as they are processes that rely on the same biological pathways. These pathways may also shed light on the pathogenesis of chronic pustular inflammatory dermatoses (e.g. acne vulgaris). The existence of safety signals from commensal bacteria, which prevent initiation of these pathways, may provide opportunities for novel therapeutic approaches to the treatment of inflammatory skin diseases.

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Section: Immune Mechanisms Of Allergic Contact Dermatitis Incorporatimentioning

confidence: 99%

Section: Immune Mechanisms Of Allergic Contact Dermatitis Incorporatimentioning

confidence: 99%

Why does allergic contact dermatitis exist?

McFadden

Puangpet

Basketter

et al. 2013

British Journal of Dermatology

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“…Interestingly the frequency of dendritic cells also increased following exposure to the highest concentration of triclosan in the DLN. Dendritic cells, derived from hematopoietic bone marrow progenitor cells, are extremely important initiators and regulators of immune responses due to their critical role in transferring information about the environment to the adaptive immune system (Ainscough et al, 2013). Previous studies conducted in our laboratory have shown that dermal exposure to triclosan – while not allergenic alone – can augment allergic responses to ovalbumin in a mouse model of asthma (Anderson et al, 2013a).…”

Section: Discussionmentioning

confidence: 99%

Investigations of immunotoxicity and allergic potential induced by topical application of triclosan in mice

Anderson

Meade

Long

et al. 2015

Journal of Immunotoxicology

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Triclosan is an antimicrobial chemical commonly used occupationally and by the general public. Using select immune function assays, the purpose of these studies was to evaluate the immunotoxicity of triclosan following dermal exposure using a murine model. Triclosan was not identified to be a sensitizer in the murine local lymph node assay (LLNA) when tested at concentrations ranging from 0.75–3.0%. Following a 28-day exposure, triclosan produced a significant increase in liver weight at concentrations of ≥ 1.5%. Exposure to the high dose (3.0%) also produced a significant increase in spleen weights and number of platelets. The absolute number of B-cells, T-cells, dendritic cells and NK cells were significantly increased in the skin draining lymph node, but not the spleen. An increase in the frequency of dendritic cells was also observed in the lymph node following exposure to 3.0% triclosan. The IgM antibody response to sheep red blood cells (SRBC) was significantly increased at 0.75% – but not at the higher concentrations – in the spleen and serum. These results demonstrate that dermal exposure to triclosan induces stimulation of the immune system in a murine model and raise concerns about potential human exposure.

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“…The skin sensitisation AOP captures the impact of skin exposure to sensitising chemicals as a series of biological and chemical key events, which have been reviewed extensively, e.g. by Ainscough et al (2013), Kimber et al (2012), Martin et al (2011), andToebak et al (2009). In brief, as a prerequisite, the chemical sensitizer needs to penetrate the stratum corneum as the uppermost layer of the skin in order to become available to the viable cells of the epidermis.…”

Section: Introductionmentioning

confidence: 99%

Systematic evaluation of non-animal test methods for skin sensitisation safety assessment

Reisinger

Hoffmann²,

Alépée

et al. 2015

Toxicology in Vitro

120

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The need for non-animal data to assess skin sensitisation properties of substances, especially cosmetics ingredients, has spawned the development of many in vitro methods. As it is widely believed that no single method can provide a solution, the Cosmetics Europe Skin Tolerance Task Force has defined a three-phase framework for the development of a non-animal testing strategy for skin sensitization potency prediction. The results of the first phase – systematic evaluation of 16 test methods – are presented here. This evaluation involved generation of data on a common set of ten substances in all methods and systematic collation of information including the level of standardisation, existing test data,potential for throughput, transferability and accessibility in cooperation with the test method developers.A workshop was held with the test method developers to review the outcome of this evaluation and to discuss the results. The evaluation informed the prioritisation of test methods for the next phase of the non-animal testing strategy development framework. Ultimately, the testing strategy – combined with bioavailability and skin metabolism data and exposure consideration – is envisaged to allow establishment of a data integration approach for skin sensitisation safety assessment of cosmetic ingredients.

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Danger, intracellular signaling, and the orchestration of dendritic cell function in skin sensitization

Cited by 40 publications

References 87 publications

Why does allergic contact dermatitis exist?

Why does allergic contact dermatitis exist?

Investigations of immunotoxicity and allergic potential induced by topical application of triclosan in mice

Systematic evaluation of non-animal test methods for skin sensitisation safety assessment

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