The role of the innate immune system in allergic contact dermatitis*

Abstract. Allergic contact dermatitis is a Tcell mediated inflammatory skin disease that is caused by low molecular weight chemicals and metal ions. These contact allergens induce skin inflammation, an essential element of the sensitization process. Our understanding of the molecular mechanisms that underlie chemical-induced inflammation has improved significantly over the last years. The emerging picture shows that contact allergens activate known innate immune and stress responses that play a role in immune responses to infections. Contact allergens use innate immune receptors such as the Toll-like receptors TLR2 and TLR4 and the NOD-like receptor NLRP3 as part of the inflammasome as well as the induction of oxidative stress to induce skin inflammation. The detailed identification of the relevant signaling pathways and the mechanisms of their activation by contact allergens will most likely lead to more targeted therapeutic approaches by interference with these pathways. Moreover, this will help to refine existing, and to develop new in vitro assays for the identification of contact allergens, an important step to replace animal testing e.g. for ingredients of cosmetics which has been prohibited now by EU legislation.