Assessment of contact allergens by dissociation of irritant and sensitizing properties

Jacobs, John J. L.; Lehé, Cynthia; Cammans, Keith D.A; Das, Pranab K.; Elliott, Graham R.

doi:10.1016/j.tiv.2004.03.007

Cited by 20 publications

(30 citation statements)

References 37 publications

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“…After removing s.c. fatty tissue, 5-mm skin punch-biopsies were cultured in RPMI 1640 containing 10% FCS, 1% pyruvate, 1% HEPES, and penicillin/ streptomycin (referred to as medium) as described (13,14), with combinations of the following soluble factors: 20 ng/ml TNF-␣, 10 ng/ml IL-1␣, 100 ng/ml IL-4, 100 ng/ml IL-5, 100 ng/ml IL-13, 1000 U/ml IFN-␥, 5 ng/ml TGF-␤, 100 ng/ml IL-10, and 10 g/ml anti-TGF-␤ blocking mAb (all obtained from R&D Systems) or 2 g/ml ALK5 inhibitor I (Calbiochem). After 48 h, culture supernatants and skin samples were collected and frozen at Ϫ80°C until assayed.…”

Section: Cell and Tissue Culturementioning

confidence: 99%

Cutting Edge: Proinflammatory and Th2 Cytokines Synergize to Induce Thymic Stromal Lymphopoietin Production by Human Skin Keratinocytes

Bogiatzi

Fernandez

Bichet

et al. 2007

The Journal of Immunology

245

203

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Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that strongly activates dendritic cells (DC) and can initiate allergic inflammation. The factors inducing the production of human TSLP are not known. In this study, we show that proinflammatory (TNF-α or IL-1α) and Th2 (IL-4 or IL-13) cytokines synergized to induce the production of TSLP in human skin explants. TSLP production in situ was restricted to epidermal keratinocytes of the suprabasal layer. TSLP production could not be inhibited by factors regulating Th2 inflammation, such as IL-10, TGF-β, or IFN-γ. Cytokine-treated skin culture supernatants induced the maturation of blood CD11c+ DC in a TSLP-dependent manner. Our data provide the first evidence of TSLP induction and subsequent DC activation in human skin. Blocking TSLP-inducing cytokines could represent a novel strategy for the treatment of allergic diseases.

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Section: Cell and Tissue Culturementioning

confidence: 99%

Cutting Edge: Proinflammatory and Th2 Cytokines Synergize to Induce Thymic Stromal Lymphopoietin Production by Human Skin Keratinocytes

Bogiatzi

Fernandez

Bichet

et al. 2007

The Journal of Immunology

245

203

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“…LC migration in human skin biopsies has been successfully used to distinguish allergens from irritants and to assess allergen potency [164, 165]. However, as an ex vivo method it is laborious and unsuitable for high throughput screenings because of the limited availability of suitable human skin.…”

Section: Introductionmentioning

confidence: 99%

Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects

Peiser

Tralau

Heidler

et al. 2011

Cell. Mol. Life Sci.

321

214

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Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German ‘Federal Institute for Risk Assessment’ hosted an ‘International Workshop on Contact Dermatitis’. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15–20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed.

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“…In contrast to allergen exposure, irritant exposure does not induce maturation-related CXCR4 (chemokine (C-X-C motif) receptor 4) and CCR7 (chemokine (C-C motif) receptor 7) expression on the surface of LCs (Yanagihara et al, 1998;Rustemeyer et al, 2003;Ouwehand et al, 2008), thereby rendering LCs unable to migrate toward the afferent lymphatics via the two-step CXCR4-CXCL12-and CCR7-CCL19/CCL21-dependent model proposed for allergen-induced LC migration (Cumberbatch et al, 2002;Jacobs et al, 2004;Ouwehand et al, 2008;Villablanca and Mora 2008). Interestingly, Marks et al (1987) showed a decrease in CD1a þ cells in the epidermis and an increase in CD1a þ cells in the dermis 2 days after patch testing volunteers with 10% SDS.…”

Section: Introductionmentioning

confidence: 99%

Irritant-Induced Migration of Langerhans Cells Coincides with an IL-10-Dependent Switch to a Macrophage-Like Phenotype

Ouwehand

Oosterhoff

Breetveld

et al. 2011

Journal of Investigative Dermatology

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Langerhans cells (LCs) migrate after topical exposure of the skin to irritants, despite the supposed independence of irritant contact dermatitis from adaptive immunity. Whereas allergen-activated LCs are known to migrate to the draining lymph nodes (LNs), the fate of migrated LCs upon topical irritant exposure is unknown. Here, we identified a phenotypic switch of LCs after their migration into the dermis upon irritant exposure. With the aid of ex vivo intact human skin and epidermal sheets, we show that dermal fibroblasts are necessary for an IL-10-dependent postmigrational phenotypic switch of LCs into macrophage-like cells. Exposure of ex vivo skin to a panel of seven irritants resulted in a decrease in the number of CD1a(+) cells and an increase in CD14(+)/CD68(+) cells in the dermis. Neutralizing antibodies against IL-10 totally inhibited the phenotypic LC-to-macrophage transition, but did not influence the migration of CD1a(+) cells. Exposure of epidermal sheets to irritants resulted in a fibroblast-dependent LC-to-CD14(+)/CD68(+) switch coinciding with migration, which could be totally inhibited by neutralizing antibodies against either IL-10 or CCL2/CCL5 (two chemokines responsible for epidermal-to-dermal migration). We have thus identified an IL-10-dependent phenotypic switch of LCs into macrophage-like cells upon irritant exposure and emigration from the epidermis.

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Assessment of contact allergens by dissociation of irritant and sensitizing properties

Cited by 20 publications

References 37 publications

Cutting Edge: Proinflammatory and Th2 Cytokines Synergize to Induce Thymic Stromal Lymphopoietin Production by Human Skin Keratinocytes

Cutting Edge: Proinflammatory and Th2 Cytokines Synergize to Induce Thymic Stromal Lymphopoietin Production by Human Skin Keratinocytes

Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects

Irritant-Induced Migration of Langerhans Cells Coincides with an IL-10-Dependent Switch to a Macrophage-Like Phenotype

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