**8. References**


Murine models of allergic and irritant skin inflammation have shed light into the pathogenesis of human contact dermatitis. They have highlighted the role of innate and adaptive immunity in allergic reactions to epicutaneously introduced allergens. More importantly, they allowed an in-depth dissection of cellular and molecular mechanisms involved in the development of the disease and will hopefully lead to new therapeutic

This work was supported by the ANRS (Agence Nationale de la recherche contre le SIDA et les hepatites virales), Fondation Recherche Medicale (FRM) and Fondation de France.

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**6. Conclusions** 

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**3** 

*The Netherlands* 

**Keratinocytes, Innate Immunity and Allergic** 

**Development of** *In Vitro* **Assays to Predict the** 

Allergic contact dermatitis (ACD) is the most prevalent form of immunotoxicity in humans characterized by clinical manifestations such as red rashes, itchy skin and blisters. The disease is caused by skin sensitizers which are allergenic low-molecular weight chemicals. ACD is an important occupational disease that gives problems at different workplaces, including hair dressers, metal workers, construction workers, and cleaners. In addition, ACD can develop in the general population as well, since several consumer products contain skin sensitizers. Important skin sensitizers are metals (nickel, chromium), fragrances, hair dye ingredients and preservatives (Kimber et al., 2002a; Vandebriel & van

ACD is a typical type IV (delayed-type) hypersensitivity response that develops in two phases, the initiation phase in which the immune system is sensitized and the elicitation phase in which the clinical symptoms develop. At initiation, the low-molecular weight and polarity of skin sensitizers allow for penetration of the stratum corneum of the skin. In addition, protein reactivity is a hallmark of skin sensitizers. After binding to proteins in the skin, hapten-carrier complexes are formed (Kimber et al., 2002a; Berard et al., 2003; Vandebriel & van Loveren, 2010). The formation of these hapten-protein complexes is crucial, since the chemicals themselves are not immunogenic and priming of T cells can only occur after formation of these complexes. After taking up these hapten-carrier complexes, immature Langerhans cells and dendritic cells start to migrate to the draining lymph node and become potent T cell activators through the upregulation of costimulatory molecules (Gaspari, 1997; Kimber et al., 2002a; Berard et al., 2003; Vocanson et al., 2009; Vandebriel & van Loveren, 2010). Hapten specific T cells are activated through a combination of haptenized peptide presentation on major histocompatibility complex (MHC) molecules and costimulatory molecules, such as CD54, CD80 and CD86. Activated T cells undergo clonal expansion, thereby generating skin homing CD8+ Tc1/Tc17 and CD4+ Th1/Th17 effector T

**1. Introduction** 

Loveren, 2010).

**Contact Dermatitis - Opportunities for the** 

*1Maastricht University, Department of Toxicogenomics, The Netherlands* 

**Sensitizing Potential of Chemicals** 

Jochem W. van der Veen1,2, Rob J. Vandebriel2, Henk van Loveren1,2 and Janine Ezendam2

*2National Institute for Public Health and the Environment,* 

of TH17/TH1 and regulatory T cells. *J. Allergy Clin. Immunol* Aug;126(2):280-289, 289.e1-7.

