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ToxSci Advance Access originally published online on July 13, 2005
Toxicological Sciences 2005 88(1):4-11; doi:10.1093/toxsci/kfi245
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

REVIEW

Interactions of Contact Allergens with Dendritic Cells: Opportunities and Challenges for the Development of Novel Approaches to Hazard Assessment

Cindy A. Ryan*,1, G. Frank Gerberick*, Lucy A. Gildea*, Ben C. Hulette*, Catherine J. Betts{dagger}, Marie Cumberbatch{dagger}, Rebecca J. Dearman{dagger} and Ian Kimber{dagger}

* Miami Valley Innovation Center, Central Product Safety Department, The Procter & Gamble Company, Cincinnati, Ohio 45253, and {dagger} Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK

Received May 10, 2005; accepted June 22, 2005

The identification of potential skin sensitizing chemicals is a key step in the overall skin safety risk assessment process. Traditionally, predictive testing has been conducted in guinea pigs. More recently, the murine local lymph node assay (LLNA) has become the preferred test method for assessing skin sensitization potential. However, even with the significant animal welfare benefits provided by the LLNA, there is a need to develop nonanimal test methods for skin sensitization. Mechanistic understanding of allergic contact dermatitis has increased substantially in recent years. For example, a number of changes are known to occur in epidermal Langerhans cells, the principal antigen-presenting dendritic cell in the skin, as a result of exposure to chemical allergens, including the internalization of surface major histocompatibility complex (MHC) class II molecules via endocytosis, the induction of tyrosine phosphorylation, the modulation of cell surface markers, and cytokine expression. The application of this knowledge to the design of predictive in vitro alternative tests provides both unique opportunities and challenges. In this review, we have focused specifically on the impact of chemical exposure on dendritic cells and the potential use of that information in the development of cell-based assays for assessing skin sensitization potential of chemicals in vitro.

Key Words: contact allergy; dendritic cells; in vitro method.


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